Reduction in Muscarinic M^sub 1^-Mediated Hypercholinergic State and Beneficial Cognitive Effects of Muscarinic Agonists in Schizophrenia/Drs. Lieberman, Javitch, and Moore Reply/Drs. Shekhar, McKinzie, and Felder Reply

摘要

Reported effects of the chronic administration of xanomeline and other compounds with M^sub 4^ agonism include a reduction in the proportion of spontaneously active dopamine neurons in the ventral tegmental area (2, 3) - an effect that would be predicted based on studies of other antipsychotic drugs -leading to decreased dopamine efflux in the striatum (4). In a number of studies, schizophrenia patients have exhibited decreased binding at M^sub 1^ and M^sub 4^ receptors, an effect consistent with chronically increased extracellular levels of acetylcholine (8).n Interestingly, preclinical testing of another M^sub 4^ receptor agonist, BuTAC, demonstrated that it possesses antipsychoticlike properties similar to xanomeline.