|
Compound was tested for its inhibitory activity against 5-hydroxytryptamine receptor
|
Rattus norvegicus
|
44.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Compound was tested for its binding affinity towards brain (Hippocampus) Adenylate cyclase
|
Cavia porcellus
|
53.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Compound was tested for its binding affinity towards brain (neocortex) Adenylate cyclase
|
Cavia porcellus
|
60.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Compound was tested for its inhibitory activity against Alpha-1 adrenergic receptor
|
None
|
0.02
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Concentration required to reducing the histamine induced contraction by 50% was measured
|
Cavia porcellus
|
0.0083
ug.mL-1
|
|
Journal : J. Med. Chem.
Title : Synthesis and antidepressant activity of substituted (omega-aminoalkoxy)benzene derivatives.
Year : 1981
Volume : 24
Issue : 2
First Page : 145
Last Page : 148
Authors : Kikumoto R, Tobe A, Tonomura S.
Abstract : A series of substituted (omega-aminoalkoxy)benzene derivatives has been synthesized and screened for potential antidepressant activities. The effect of structural variation of these molecules has been systematically examined. Antidepressant activity was clearly displayed by 2-benzyl-1-[4-(methylamino)butoxy]benzene (7), 2-(2-hydroxybenzyl)-1-[4-(methylamino)butoxy]benzene (19), 1-[4-(methylamino)butoxy]-2-phenoxybenzene (29), and 1-[4-(methylamino)butoxy]-2-(phenylthio)benzene (31) in further pharmacological studies. These compounds did not possess the anticholinergic, antihistaminic, and muscle-relaxant side effects common to tricyclic antidepressants.
|
Compound tested for its inhibitory activity against Histamine H1 receptor
|
None
|
0.02
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Inhibitory activity against brain adenylate cyclase Histamine H2 receptor
|
Cavia porcellus
|
660.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
Inhibition of radioligand [3H]QNB binding to muscarinic acetylcholine receptor in the rat forebrain in the presence of zinc
|
None
|
300.0
nM
|
|
Journal : J. Med. Chem.
Title : Substituted (pyrroloamino)pyridines: potential agents for the treatment of Alzheimer's disease.
Year : 1996
Volume : 39
Issue : 2
First Page : 582
Last Page : 587
Authors : Davis L, Olsen GE, Klein JT, Kapples KJ, Huger FP, Smith CP, Petko WW, Cornfeldt M, Effland RC.
Abstract : A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Compounds displaying significant activity were more broadly evaluated, which revealed the presence of a desirable adrenergic component of activity. The synthesis and structure-activity relationships for this series is presented, along with the biological profiles of selected compounds.
|
Compound was tested for its inhibitory activity against Noradrenaline receptor
|
Rattus norvegicus
|
41.0
nM
|
|
Journal : J. Med. Chem.
Title : Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography.
Year : 1999
Volume : 42
Issue : 16
First Page : 3154
Last Page : 3162
Authors : Quiñones-Torrelo C, Sagrado S, Villanueva-Camañas RM, Medina-Hernández MJ.
Abstract : The distribution of tricyclic antidepressants from plasma to brain, where these drugs exert their main clinical action, and other organs is related to transport events across the cell membranes of the different tissues. It could be expected that all the molecular features that condition the transport processes (mainly hydrophobicity and molar total charge) also control the pharmacokinetic and biochemical behavior. Micellar liquid chromatography (MLC) has been proposed to emulate in vitro the partitioning process in the biomembranes. The use of micellar solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of local anesthetics, barbiturates, catecholamines, and benzodiazepines. In this paper, the relationships between the capacity factor in MLC and some pharmacokinetic parameters and biological responses of tricyclic antidepressants are studied. Predictive regression models for the estimation of these parameter values, using the logarithm of the retention data (log k) as independent variable, are also proposed.
|
In vitro inhibition of the accumulation of (-)-[3H]-5-HT in synaptosomes from the rat brain cortex
|
Rattus norvegicus
|
320.0
nM
|
|
Journal : J. Med. Chem.
Title : Homoallylic amines related to zimeldine. A comparative study on neuronal serotonin and norepinephrine reuptake based on conformational analysis.
Year : 1988
Volume : 31
Issue : 5
First Page : 913
Last Page : 919
Authors : Högberg T, Ross SB, Ström P, Grunewald GL, Creese MW, Bunce JD.
Abstract : A number of tertiary and secondary homoallylic amines, i.e. (Z)- and (E)-4-(4-bromophenyl)-4-(3-pyridyl)-3-buten-1-ylamines, were synthesized in diastereomerically pure forms. The compounds were evaluated as neuronal norepinephrine (NE) and serotonin (5-HT) uptake inhibitors under in vitro and ex vivo conditions and compared with the tricyclics amitriptyline and nortriptyline having homoallylic side chains and with the corresponding diastereomers in the zimeldine series having allylic side chains. The Z isomers of the new homoallylic derivatives (3Z, 4Z) were specific 5-HT uptake inhibitors in analogy with the corresponding allylic derivatives zimeldine (1Z) and norzimeldine (2Z). Likewise, the selectivity profile of the homoallylic (3E, 4E) and the allylic (1E, 2E) derivatives was comparable. In general, the homoallylic compounds were less potent inhibitors than their allylic counterparts. The similarities and discrepancies were evaluated in terms of conformational preferences determined by CAMSEQ molecular mechanics calculations. Homonorzimeldine (4Z) can accommodate energetically favored, but less populated, conformations having amino nitrogen atom to aromatic ring center distances comparable to those in norzimeldine. These facts correlate to retained 5-HT selectivity but diminished potency of 4Z compared to 2Z.
|
In vitro inhibition of the accumulation of (-)-[3H]Norepinephrine in synaptosomes from the rat brain cortex
|
Rattus norvegicus
|
61.0
nM
|
|
Journal : J. Med. Chem.
Title : Homoallylic amines related to zimeldine. A comparative study on neuronal serotonin and norepinephrine reuptake based on conformational analysis.
Year : 1988
Volume : 31
Issue : 5
First Page : 913
Last Page : 919
Authors : Högberg T, Ross SB, Ström P, Grunewald GL, Creese MW, Bunce JD.
Abstract : A number of tertiary and secondary homoallylic amines, i.e. (Z)- and (E)-4-(4-bromophenyl)-4-(3-pyridyl)-3-buten-1-ylamines, were synthesized in diastereomerically pure forms. The compounds were evaluated as neuronal norepinephrine (NE) and serotonin (5-HT) uptake inhibitors under in vitro and ex vivo conditions and compared with the tricyclics amitriptyline and nortriptyline having homoallylic side chains and with the corresponding diastereomers in the zimeldine series having allylic side chains. The Z isomers of the new homoallylic derivatives (3Z, 4Z) were specific 5-HT uptake inhibitors in analogy with the corresponding allylic derivatives zimeldine (1Z) and norzimeldine (2Z). Likewise, the selectivity profile of the homoallylic (3E, 4E) and the allylic (1E, 2E) derivatives was comparable. In general, the homoallylic compounds were less potent inhibitors than their allylic counterparts. The similarities and discrepancies were evaluated in terms of conformational preferences determined by CAMSEQ molecular mechanics calculations. Homonorzimeldine (4Z) can accommodate energetically favored, but less populated, conformations having amino nitrogen atom to aromatic ring center distances comparable to those in norzimeldine. These facts correlate to retained 5-HT selectivity but diminished potency of 4Z compared to 2Z.
|
Inhibition of binding of Batrachotoxinin [3H]BTX-B to high affinity sites on voltage dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex at 10 uM
|
Cavia porcellus
|
73.8
%
|
|
Journal : J. Med. Chem.
Title : [3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs.
Year : 1985
Volume : 28
Issue : 3
First Page : 381
Last Page : 388
Authors : McNeal ET, Lewandowski GA, Daly JW, Creveling CR.
Abstract : [3H]Batrachotoxinin A benzoate ( [3H]BTX-B) binds with high affinity to sites on voltage-dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex. In this preparation, local anesthetics competitively antagonize the binding of [3H]BTX-B. The potencies of some 40 classical local anesthetics and a variety of catecholamine, histamine, serotonin, adenosine, GABA, glycine, acetylcholine, and calcium antagonists, tranquilizers, antidepressants, barbiturates, anticonvulsants, steroids, vasodilators, antiinflammatories, anticoagulants, analgesics, and other agents have been determined. An excellent correlation with the known local anesthetic activity of many of these agents indicate that antagonism of binding of [3H]BTX-B binding provides a rapid, quantitative, and facile method for the screening and investigation of local anesthetic activity.
|
Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells at 100 uM by confocal microscopy
|
Homo sapiens
|
78.5
%
|
|
Journal : J. Med. Chem.
Title : Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1.
Year : 2008
Volume : 51
Issue : 19
First Page : 5932
Last Page : 5942
Authors : Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergström CA, Artursson P.
Abstract : The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral drugs with the aim of studying the inhibition pattern of OCT1 and of developing predictive computational models of OCT1 inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
|
Displacement of [3H]pyrilamine from human histamine H1 receptor expressed in CHO cells
|
Homo sapiens
|
1.12
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics.
Year : 2009
Volume : 19
Issue : 2
First Page : 538
Last Page : 542
Authors : von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H.
Abstract : Histamine H3 receptor (H3R) antagonists have some antipsychotic properties although the clear molecular mechanism is still unknown. As actually the most effective and less side effective antipsychotics are drugs with multiple targets we have designed typical and atypical neuroleptics with an additional histamine H3 pharmacophore. The 4-(3-piperidinopropoxy)phenyl pharmacophore moiety has been linked to amitriptyline, maprotiline, chlorpromazine, chlorprothixene, fluphenazine, and clozapine. Amide, amine and ester elements have been used generally to maintain or slightly shift affinity at dopamine D(2)-like receptors (D2 and D3), to decrease affinity at histamine H(1) receptors, and to obtain H3R ligands with low nanomolar or subnanomolar affinity. Change of effects at D(1)-like receptors (D1) and (D5) were heterogeneous. With these newly profiled compounds different antipsychotic properties might be achieved.
|
Displacement of [3H]SCH23390 from human dopamine D1 receptor expressed in HEK cells
|
Homo sapiens
|
89.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics.
Year : 2009
Volume : 19
Issue : 2
First Page : 538
Last Page : 542
Authors : von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H.
Abstract : Histamine H3 receptor (H3R) antagonists have some antipsychotic properties although the clear molecular mechanism is still unknown. As actually the most effective and less side effective antipsychotics are drugs with multiple targets we have designed typical and atypical neuroleptics with an additional histamine H3 pharmacophore. The 4-(3-piperidinopropoxy)phenyl pharmacophore moiety has been linked to amitriptyline, maprotiline, chlorpromazine, chlorprothixene, fluphenazine, and clozapine. Amide, amine and ester elements have been used generally to maintain or slightly shift affinity at dopamine D(2)-like receptors (D2 and D3), to decrease affinity at histamine H(1) receptors, and to obtain H3R ligands with low nanomolar or subnanomolar affinity. Change of effects at D(1)-like receptors (D1) and (D5) were heterogeneous. With these newly profiled compounds different antipsychotic properties might be achieved.
|
Displacement of [3H]SCH23390 from human dopamine D5 receptor expressed in HEK cells
|
Homo sapiens
|
170.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics.
Year : 2009
Volume : 19
Issue : 2
First Page : 538
Last Page : 542
Authors : von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H.
Abstract : Histamine H3 receptor (H3R) antagonists have some antipsychotic properties although the clear molecular mechanism is still unknown. As actually the most effective and less side effective antipsychotics are drugs with multiple targets we have designed typical and atypical neuroleptics with an additional histamine H3 pharmacophore. The 4-(3-piperidinopropoxy)phenyl pharmacophore moiety has been linked to amitriptyline, maprotiline, chlorpromazine, chlorprothixene, fluphenazine, and clozapine. Amide, amine and ester elements have been used generally to maintain or slightly shift affinity at dopamine D(2)-like receptors (D2 and D3), to decrease affinity at histamine H(1) receptors, and to obtain H3R ligands with low nanomolar or subnanomolar affinity. Change of effects at D(1)-like receptors (D1) and (D5) were heterogeneous. With these newly profiled compounds different antipsychotic properties might be achieved.
|
Displacement of [3H]spiperone from human dopamine D2 receptor expressed in CHO cells
|
Homo sapiens
|
196.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics.
Year : 2009
Volume : 19
Issue : 2
First Page : 538
Last Page : 542
Authors : von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H.
Abstract : Histamine H3 receptor (H3R) antagonists have some antipsychotic properties although the clear molecular mechanism is still unknown. As actually the most effective and less side effective antipsychotics are drugs with multiple targets we have designed typical and atypical neuroleptics with an additional histamine H3 pharmacophore. The 4-(3-piperidinopropoxy)phenyl pharmacophore moiety has been linked to amitriptyline, maprotiline, chlorpromazine, chlorprothixene, fluphenazine, and clozapine. Amide, amine and ester elements have been used generally to maintain or slightly shift affinity at dopamine D(2)-like receptors (D2 and D3), to decrease affinity at histamine H(1) receptors, and to obtain H3R ligands with low nanomolar or subnanomolar affinity. Change of effects at D(1)-like receptors (D1) and (D5) were heterogeneous. With these newly profiled compounds different antipsychotic properties might be achieved.
|
Displacement of [3H]spiperone from human dopamine D3 receptor expressed in CHO cells
|
Homo sapiens
|
206.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics.
Year : 2009
Volume : 19
Issue : 2
First Page : 538
Last Page : 542
Authors : von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H.
Abstract : Histamine H3 receptor (H3R) antagonists have some antipsychotic properties although the clear molecular mechanism is still unknown. As actually the most effective and less side effective antipsychotics are drugs with multiple targets we have designed typical and atypical neuroleptics with an additional histamine H3 pharmacophore. The 4-(3-piperidinopropoxy)phenyl pharmacophore moiety has been linked to amitriptyline, maprotiline, chlorpromazine, chlorprothixene, fluphenazine, and clozapine. Amide, amine and ester elements have been used generally to maintain or slightly shift affinity at dopamine D(2)-like receptors (D2 and D3), to decrease affinity at histamine H(1) receptors, and to obtain H3R ligands with low nanomolar or subnanomolar affinity. Change of effects at D(1)-like receptors (D1) and (D5) were heterogeneous. With these newly profiled compounds different antipsychotic properties might be achieved.
|
DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
11.0
nM
|
|
DRUGMATRIX: Muscarinic M1 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
2.724
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
81.0
nM
|
|
DRUGMATRIX: Muscarinic M2 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
29.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
26.0
nM
|
|
DRUGMATRIX: Muscarinic M3 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
5.436
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
5.297
nM
|
|
DRUGMATRIX: Muscarinic M4 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
0.739
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
8.02
nM
|
|
DRUGMATRIX: Muscarinic M5 radioligand binding (ligand: [3H] N-Methylscopolamine)
|
None
|
5.762
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
15.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
4.374
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
14.0
nM
|
|
DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
5.599
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
76.0
nM
|
|
DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
42.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
105.0
nM
|
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
52.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
351.0
nM
|
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
132.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
8.076
nM
|
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
3.687
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
59.0
nM
|
|
DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
8.599
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
23.0
nM
|
|
DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
22.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
70.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
45.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
6.048
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
3.168
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
140.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
65.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
1.661
nM
|
|
DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
0.882
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Sigma1 radioligand binding (ligand: [3H] Haloperidol)
|
None
|
433.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
840.0
nM
|
|
DRUGMATRIX: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
816.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
355.0
nM
|
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
178.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone)
|
None
|
336.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
182.0
nM
|
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
62.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)
|
None
|
4.782
nM
|
|
DRUGMATRIX: Histamine H1, Central radioligand binding (ligand: [3H] Pyrilamine)
|
None
|
0.555
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Histamine H2 radioligand binding (ligand: [125I] Aminopotentidine)
|
None
|
730.0
nM
|
|
DRUGMATRIX: Histamine H2 radioligand binding (ligand: [125I] Aminopotentidine)
|
None
|
718.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
TP_TRANSPORTER: increase in Calcein-AM intracellular accumulation (Calcein-AM: ? uM, Amitriptyline: 100 uM) in MDR1-expressing MDCKII cells
|
None
|
25.5
%
|
|
Journal : J. Pharmacol. Exp. Ther.
Title : Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs.
Year : 2002
Volume : 303
Issue : 1
First Page : 1029
Last Page : 1037
Authors : Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW.
Abstract : Membrane permeability and P-glycoprotein (Pgp) can be limiting factors for blood-brain barrier penetration. The objectives of this study were to determine whether there are differences in the in vitro permeability, Pgp substrate profiles, and physicochemical properties of drugs for central nervous system (CNS) and non-CNS indications, and whether these differences are useful criteria in selecting compounds for drug development. Apparent permeability (P(app)) and Pgp substrate profiles for 93 CNS (n = 48) and non-CNS (n = 45) drugs were determined by monolayer efflux. Calcein-AM inhibition assays were used to supplement the efflux results. The CNS set (2 of 48, 4.2%) had a 7-fold lower incidence of passive permeability values <150 nm/s compared with the non-CNS set (13 of 45, 28.9%). The majority of drugs (72.0%, 67 of 93) were not Pgp substrates; however, 49.5% (46 of 93) were positive in the calcein-AM assay when tested at 100 microM. The CNS drug set (n = 7 of 48, 14.6%) had a 3-fold lower incidence of Pgp-mediated efflux than the non-CNS drug set (n = 19 of 45, 42.2%). Analysis of 18 physicochemical properties revealed that the CNS drug set had fewer hydrogen bond donors, fewer positive charges, greater lipophilicity, lower polar surface area, and reduced flexibility compared with the non-CNS group (p < 0.05), properties that enhance membrane permeability. This study on a large, diverse set of marketed compounds clearly demonstrates that permeability, Pgp-mediated efflux, and certain physicochemical properties are factors that differentiate CNS and non-CNS drugs. For CNS delivery, a drug should ideally have an in vitro passive permeability >150 nm/s and not be a good (B --> A/A --> B ratio <2.5) Pgp substrate.
|
Inhibition of human liver OATP1B1 expressed in HEK293 Flp-In cells assessed as reduction in E17-betaG uptake at 20 uM by scintillation counting
|
Homo sapiens
|
10.5
%
|
|
Journal : J. Med. Chem.
Title : Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
Year : 2012
Volume : 55
Issue : 10
First Page : 4740
Last Page : 4763
Authors : Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P.
Abstract : The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.
|
Inhibition of human liver OATP1B3 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E17-betaG uptake at 20 uM incubated for 5 mins by scintillation counting
|
Homo sapiens
|
22.0
%
|
|
Journal : J. Med. Chem.
Title : Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
Year : 2012
Volume : 55
Issue : 10
First Page : 4740
Last Page : 4763
Authors : Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P.
Abstract : The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.
|
Inhibition of human liver OATP2B1 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E3S uptake at 20 uM incubated for 5 mins by scintillation counting
|
Homo sapiens
|
-8.9
%
|
|
Journal : J. Med. Chem.
Title : Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
Year : 2012
Volume : 55
Issue : 10
First Page : 4740
Last Page : 4763
Authors : Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P.
Abstract : The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions. Predicting potential interactions with OATPs is, therefore, of value. Here, we developed in vitro and in silico models for identification and prediction of specific and general inhibitors of OATP1B1, OATP1B3, and OATP2B1. The maximal transport activity (MTA) of each OATP in human liver was predicted from transport kinetics and protein quantification. We then used MTA to predict the effects of a subset of inhibitors on atorvastatin uptake in vivo. Using a data set of 225 drug-like compounds, 91 OATP inhibitors were identified. In silico models indicated that lipophilicity and polar surface area are key molecular features of OATP inhibition. MTA predictions identified OATP1B1 and OATP1B3 as major determinants of atorvastatin uptake in vivo. The relative contributions to overall hepatic uptake varied with isoform specificities of the inhibitors.
|
Inhibition of [3H]5-HT uptake at human SERT expressed in HEK293 cells preincubated for 10 mins prior to substrate addition measured after 4 mins by FLIPR assay
|
Homo sapiens
|
141.0
nM
|
|
Inhibition of [3H]5-HT uptake at human SERT expressed in HEK293 cells preincubated for 10 mins prior to substrate addition measured after 4 mins by FLIPR assay
|
Homo sapiens
|
549.54
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
Year : 2013
Volume : 23
Issue : 11
First Page : 3411
Last Page : 3415
Authors : Arunotayanun W, Dalley JW, Huang XP, Setola V, Treble R, Iversen L, Roth BL, Gibbons S.
Abstract : Novel Psychoactive Drugs (NPD) can be sold without restriction and are often synthetic analogues of controlled drugs. The tryptamines are an important class of NPD as they bind to the various serotonin (5-HT) receptor subtypes and cause psychosis and hallucinations that can lead to injury or death through misadventure. Here we report on the structure elucidation and receptor binding profiles of two widely marketed tryptamine-derived NPDs, namely alpha-methyl-tryptamine and 5-methoxy-N,N-diallyl-tryptamine.
|
Inhibition of [3H]norepinephrine uptake at human NET expressed in HEK293 cells preincubated for 10 mins prior to substrate addition measured after 4 mins by FLIPR assay
|
Homo sapiens
|
333.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
Year : 2013
Volume : 23
Issue : 11
First Page : 3411
Last Page : 3415
Authors : Arunotayanun W, Dalley JW, Huang XP, Setola V, Treble R, Iversen L, Roth BL, Gibbons S.
Abstract : Novel Psychoactive Drugs (NPD) can be sold without restriction and are often synthetic analogues of controlled drugs. The tryptamines are an important class of NPD as they bind to the various serotonin (5-HT) receptor subtypes and cause psychosis and hallucinations that can lead to injury or death through misadventure. Here we report on the structure elucidation and receptor binding profiles of two widely marketed tryptamine-derived NPDs, namely alpha-methyl-tryptamine and 5-methoxy-N,N-diallyl-tryptamine.
|
Displacement of [3H]Citalopram from serotonin transporter (unknown origin)
|
Homo sapiens
|
9.55
nM
|
|
Displacement of [3H]Citalopram from serotonin transporter (unknown origin)
|
Homo sapiens
|
4.3
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : The synthesis and comparative receptor binding affinities of novel, isomeric pyridoindolobenzazepine scaffolds.
Year : 2014
Volume : 24
Issue : 2
First Page : 576
Last Page : 579
Authors : Rajagopalan R, Bandyopadhyaya A, Rajagopalan DR, Rajagopalan P.
Abstract : Compounds 7, 8, and 9, derived from the novel scaffolds 3, 5, and 6, were synthesized and evaluated in vitro. The b,c→c,d shift of the E-phenyl ring resulted in a large decrease (ca. 20- to 1000-fold) in binding to the 5-HT2A, 5-HT2C and H2, receptors, and a modest decrease (ca. 10- to 20-fold) in binding to the 5-HT5A, D2, D5, and α1D, receptors. The b,c→d,e shift resulted in a large decrease in binding to the 5-HT1D, 5-HT2C, 5-HT6, and H1 receptors, a modest decrease in binding to 5-HT1A, 5-HT5A and D2, D5, α2B, and H2 receptors, and a large increase in affinity to the 5-HT3, 5-HT6, and σ1 receptors.
|
Antiplasmodial activity against Plasmodium falciparum K1 at 0.002 to 100 ug/ml by serial drug dilution assay
|
Plasmodium falciparum K1
|
500.0
nM
|
|
Journal : Bioorg Med Chem
Title : Astemizole analogues with reduced hERG inhibition as potent antimalarial compounds.
Year : 2017
Volume : 25
Issue : 24
First Page : 6332
Last Page : 6344
Authors : Tian J, Vandermosten L, Peigneur S, Moreels L, Rozenski J, Tytgat J, Herdewijn P, Van den Steen PE, De Jonghe S.
Abstract : Astemizole is a H1-antagonist endowed with antimalarial activity, but has hERG liabilities. Systematic structural modifications of astemizole led to the discovery of analogues that display very potent activity as inhibitors of the growth of the Plasmodium parasite, but show a decreased hERG inhibition, when compared to astemizole. These compounds can be used as starting point for the development of a new class of antimalarials.
|
Inhibition of human ERG expressed in HEK293 cells at 10 uM by automated patch clamp method relative to control
|
Homo sapiens
|
97.7
%
|
|
Journal : J Nat Prod
Title : Diterpenoids from Euphorbia dulcis with Potassium Ion Channel Inhibitory Activity with Selective G Protein-Activated Inwardly Rectifying Ion Channel (GIRK) Blocking Effect.
Year : 2018
Volume : 81
Issue : 11
First Page : 2483
Last Page : 2492
Authors : Kúsz N, Orvos P, Bereczki L, Fertey P, Bombicz P, Csorba A, Tálosi L, Jakab G, Hohmann J, Rédei D.
Abstract : Nine new (1-9) and two known (10, 11) jatrophane diterpenoids were isolated from the methanol extract of Euphorbia dulcis. The structure elucidation of the compounds was performed by means of extensive spectroscopic analysis, including HRESIMS, 1D (1H, JMOD), and 2D (HSQC, HMBC, 1H-1H-COSY, NOESY) NMR experiments. The absolute configuration of compound 1 was determined by single-crystal X-ray diffraction. The electrophysiological effects of compounds 1-11 and the five diterpenoids (12-16) previously isolated from Euphorbia taurinensis were investigated on stable transfected HEK-GIRK1/4 (Kir3.1/3.4) and HEK-hERG (Kv11.1) cell lines using automated patch-clamp equipment. The majority of the diterpenoids showed significant blocking activity on GIRK channels (60.8-88.7% at 10 μM), while compounds 1, 2, 9-11, 13, and 14 exerted notable inhibitory effects even at 1 μM concentration. None of the jatrophane diterpenoids interfered with the function of hERG proteins; however, compound 14 remarkably hampered K+ flow through hERG channels. These selective activities suggest that jatrophane diterpenoids may represent a group of potential lead compounds for the development of novel therapeutic agents against atrial fibrillation.
|
Displacement of [3H]citalopram from human SERT expressed in HEK293 cells measured after 30 mins
|
Homo sapiens
|
5.4
nM
|
|
Journal : J Med Chem
Title : Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy.
Year : 2016
Volume : 59
Issue : 13
First Page : 6329
Last Page : 6343
Authors : Sun H, Shi M, Zhang W, Zheng YM, Xu YZ, Shi JJ, Liu T, Gunosewoyo H, Pang T, Gao ZB, Yang F, Tang J, Yu LF.
Abstract : A novel series of sigma (σ) receptor ligands based on an alkoxyisoxazole scaffold has been designed and synthesized. Preliminary receptor binding assays identified highly potent (Ki < 1 nM) and selective σ1 ligands devoid of binding interactions with the monoamine transporters DAT, NET, and SERT. In particular, compound 53 was shown to possess significant antinociceptive activity in the mouse formalin-induced inflammation pain model when administered intraperitoneally at 40 and 80 mg/kg. Initial pharmacokinetics evaluation indicated an excellent brain exposure following oral dosing in mice, suggesting that further investigation into the use of alkoxyisoxazoles as σ1 ligands for antinociception is warranted. This study supports the notion that selective σ1 antagonism could be a useful strategy in the development of novel antipain therapy.
|
Displacement of [3H]citalopram from human SERT expressed in HEK293 cells at 10 uM measured after 30 mins
|
Homo sapiens
|
50.0
%
|
|
Journal : J Med Chem
Title : Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy.
Year : 2016
Volume : 59
Issue : 13
First Page : 6329
Last Page : 6343
Authors : Sun H, Shi M, Zhang W, Zheng YM, Xu YZ, Shi JJ, Liu T, Gunosewoyo H, Pang T, Gao ZB, Yang F, Tang J, Yu LF.
Abstract : A novel series of sigma (σ) receptor ligands based on an alkoxyisoxazole scaffold has been designed and synthesized. Preliminary receptor binding assays identified highly potent (Ki < 1 nM) and selective σ1 ligands devoid of binding interactions with the monoamine transporters DAT, NET, and SERT. In particular, compound 53 was shown to possess significant antinociceptive activity in the mouse formalin-induced inflammation pain model when administered intraperitoneally at 40 and 80 mg/kg. Initial pharmacokinetics evaluation indicated an excellent brain exposure following oral dosing in mice, suggesting that further investigation into the use of alkoxyisoxazoles as σ1 ligands for antinociception is warranted. This study supports the notion that selective σ1 antagonism could be a useful strategy in the development of novel antipain therapy.
|
Inhibition of human ERG expressed in CHO cells at 1 uM by manual patch-clamp electrophysiology
|
Homo sapiens
|
23.15
%
|
|
|
Inhibition of human ERG expressed in CHO cells at 10 uM by manual patch-clamp electrophysiology
|
Homo sapiens
|
76.13
%
|
|
|
Displacement of [3H]-scopolamine from human recombinant muscarinic M1 receptor expressed in human recombinant CHO-K1 cells at 1 uM incubated for 120 mins by solid scintillation counting method relative to control
|
Homo sapiens
|
78.0
%
|
|
|
Displacement of [3H]-pyrilamine from human recombinant histamine H1 receptor expressed in human recombinant CHO-K1 cells at 1 uM incubated for 60 mins by solid scintillation counting method relative to control
|
Homo sapiens
|
99.0
%
|
|
|
Displacement of [3H]-prazosin from rat cortex membrane alpha1 adrenergic receptor expressed in human recombinant CHO-K1 cells at 1 uM after 30 mins by solid scintillation counting method relative to control
|
Rattus norvegicus
|
82.0
%
|
|
|
Displacement of [3H]-citalopram from human SERT expressed in HEK cell membrane assessed as inhibition constant by radioligand binding assay
|
Homo sapiens
|
9.2
nM
|
|
