Ionic regulation of antagonist binding to the human muscarinic cholinergic receptor of caudate nucleus

In this in vitro study we investigated the effects of a variety of cations on binding of the cholinergic antagonist, (3H)-quinuclidinyl benzilate, to the human caudate. Physiologic sodium concentrations induced a state of positive cooperativity upon the human muscarinic cholinergic receptor (nHill = 1.41). Lithium at therapeutic equivalency (1 mM) was unique in increasing the dissociation constant (KD) for this antagonist from 35.9 to 72.4 pM. This implies a lithium-induced cholinomimetic effect at the human muscarinic receptor consistent with reports of the reversal of mania by physostigmine. These findings are also relevant to previous cholinergic receptor studies in which various cations have been employed.