One of the take-home messages from our recent report regarding the clinical and biological effects of the atypical neuroleptic, clozapine, was that the admixture of clozapine's effects on dopaminergic, serotonergic, and noradrenergic systems may underlie its unique efficacy in otherwise poorly responsive patients with schizophrenia.1 We agree with a suggestion by R. W. Pies, MD, (unpublished communication to the Archives, May 1992) that clozapine's diverse pharmacologic properties indicate strategies for augmentation of neuroleptic drugs in treatment-resistant patients and that thioridazine or mesoridazine besylate may be particularly useful, given their relatively low incidence of extrapyramidal side effects.
Whereas much attention has been given to the 5-hydroxytryptamine2 (5-HT2) antagonism of clozapine, including the ratio of 5-HT2 to D2 affinities as a predictor of neuroleptic atypicality,2 we have noted that clozapine's relatively potent α2-antagonism (putatively contributing to observed increases in norepinephrine turnover) is distinct among
Pickar D, Litman RE, Hong WW, Su TP, Weissman EM, Hsiao JK, Potter WZ. Clinical Response to Clozapine in Patients With Schizophrenia. Arch Gen Psychiatry. 1994;51(2):159-160. doi:10.1001/archpsyc.1994.03950020083008