Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain.

Article Details

Citation

El-Fakahany E, Richelson E

Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain.

Br J Pharmacol. 1983 Jan;78(1):97-102.

PubMed ID
6297650 [ View in PubMed
]
Abstract

1 Twenty-two compounds classified as antidepressants, metabolites of antidepressants or putative antidepressants were assayed for their ability to antagonize the binding of (-)-[3H]-quinuclidinyl benzilate to muscarinic receptors in homogenates of human caudate nucleus. 2 Sixteen of these compounds were assayed for their ability to antagonize carbachol-stimulated cyclic guanosine 3',5'-monophosphate (cyclic GMP) synthesis by intact murine neuroblastoma cells (clone N1E-115). 3 Equilibrium dissociation constants (KDs) for these drugs and the muscarinic receptors of human brain spanned over 4 orders of magnitude, with the tertiary amine tricyclic antidepressant, amitriptyline (KD = 18 nM) being the most potent compound tested and trazodone (KD = 324 microM) the least potent. 4 There was a significant correlation between the data for human and murine receptors and for eight compounds (imipramine, desipramine, maprotiline, mianserin, 3-chloro-2-hydroxyimipramine, amoxapine, 2-hydroxyimipramine and iprindole). KD values measured by the two techniques were not significantly different.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MaprotilineMuscarinic acetylcholine receptor M1ProteinHumans
No
Antagonist
Details
MaprotilineMuscarinic acetylcholine receptor M2ProteinHumans
No
Antagonist
Details
MaprotilineMuscarinic acetylcholine receptor M3ProteinHumans
No
Antagonist
Details
MaprotilineMuscarinic acetylcholine receptor M4ProteinHumans
No
Antagonist
Details
MaprotilineMuscarinic acetylcholine receptor M5ProteinHumans
No
Antagonist
Details