Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain

E. El Fakahany, E. Richelson

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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. 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). Equilibrium dissociation constants (K(D)(s)) for these drugs and the muscarinic receptors of human brain spanned over 4 orders of magnitude, with the tertiary amine tricyclic antidepressant, amitriptyline (K(D) = 18 nM)) being the most potent compound tested and trazodone (K(D) = 324 μM) the least potent. 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). K(D) values measured by the two techniques were not significantly different.

Original languageEnglish (US)
Pages (from-to)97-102
Number of pages6
JournalBritish Journal of Pharmacology
Volume78
Issue number1
StatePublished - 1983

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Muscarinic Receptors
Antidepressive Agents
Iprindole
Brain
Amoxapine
Maprotiline
Quinuclidinyl Benzilate
Trazodone
Mianserin
Drug Receptors
Desipramine
Amitriptyline
Caudate Nucleus
Imipramine
Tricyclic Antidepressive Agents
Cyclic GMP
Carbachol
Neuroblastoma
Amines
Clone Cells

ASJC Scopus subject areas

  • Pharmacology

Cite this

Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. / El Fakahany, E.; Richelson, E.

In: British Journal of Pharmacology, Vol. 78, No. 1, 1983, p. 97-102.

Research output: Contribution to journalArticle

El Fakahany, E. ; Richelson, E. / Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. In: British Journal of Pharmacology. 1983 ; Vol. 78, No. 1. pp. 97-102.
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