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

Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. doi: 10.1016/0006-2952(93)90211-e.


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 microM. 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Histamine H1 Antagonists / pharmacology*
  • Humans
  • Muscarinic Antagonists*


  • Antidepressive Agents
  • Histamine H1 Antagonists
  • Muscarinic Antagonists