Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics

Tiffany Stanton, Carolyn Bolden-Watson, Bernadette Cusack, Elliott Richelson

Research output: Contribution to journalArticle

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Abstract

Based on molecular cloning studies, five different muscarinic receptor subtypes exist: m1, m2, m3, m4, and m5. We determined the affinity and selectivity of binding for sixteen antidepressants, two of their metabolites, and three antihistaminics (h1) at these subtypes. Using Chinese hamster ovary cells (CHO-K1) transfected with genes for the human muscarinic receptor subtypes, we obtained equilibrium dissociation constants (Kds) from competitive radioligand binding studies with [3H]-quinuclidinyl benzilate ([3H]QNB) and membranal preparations of these cells. QNB was the most potent compound studied (Kd 30-80 pM). Mequitazine (Kd 6-14 nM) and amitriptyline (Kd 7-16 nM) exhibited the highest affinity among the antihistaminics and antidepressants, respectively. Among the antidepressants examined were the serotonin-selective drugs sertraline and fluoxetine, both of which displayed Kd values > 1 μM. The remaining antidepressants were moderate to weak antagonists with some eliciting no radioligand competition at high concentrations. The compounds studied showed no significant selectivity among the five cloned subtypes.

Original languageEnglish (US)
Pages (from-to)2352-2354
Number of pages3
JournalBiochemical Pharmacology
Volume45
Issue number11
DOIs
StatePublished - Jun 9 1993

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CHO Cells
Cholinergic Receptors
Muscarinic Receptors
Cholinergic Agents
Antidepressive Agents
Quinuclidinyl Benzilate
Histamine H1 Antagonists
Serotonin Agents
Sertraline
Amitriptyline
Competitive Binding
Fluoxetine
Cloning
Molecular Cloning
Metabolites
Cricetulus
Ovary
Serotonin
Genes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. / Stanton, Tiffany; Bolden-Watson, Carolyn; Cusack, Bernadette; Richelson, Elliott.

In: Biochemical Pharmacology, Vol. 45, No. 11, 09.06.1993, p. 2352-2354.

Research output: Contribution to journalArticle

Stanton, Tiffany ; Bolden-Watson, Carolyn ; Cusack, Bernadette ; Richelson, Elliott. / Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. In: Biochemical Pharmacology. 1993 ; Vol. 45, No. 11. pp. 2352-2354.
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