Previous hypotheses for the superiority of clozapine over other antipsychotics have failed to stand the test of time. Here we describe how the unique pharmacology of clozapine in the peripheral nervous system held clues for solving the puzzle of clozapine in the central nervous system. Clozapine appears to have been the prototype for a new class of antipsychotics, now entering clinical psychiatry, which activates muscarinic acetylcholine receptors.
Keywords: Cobenfy; KarXT; M1; M4; Schizophrenia; acetylcholine; agonist; cholinergic; clozapine; emraclidine; mechanism; muscarinic; psychosis; receptor; striatum; xanomeline.