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Review
. 2013 Jul 17;4(7):1018-25.
doi: 10.1021/cn400121z.

Classics in chemical neuroscience: clozapine

Cody J Wenthur  1 , Craig W Lindsley
Affiliations
Review

Classics in chemical neuroscience: clozapine

Cody J Wenthur et al. ACS Chem Neurosci. .

Abstract

Clozapine was the first true breakthrough in schizophrenia treatment since the discovery of chlorpromazine in 1950, effectively treating positive, negative, and some cognitive symptoms, as well as possessing unprecedented efficacy in treatment-resistant patients. Despite over 30 years of intense study, the precise molecular underpinnings that account for clozapine's unique efficacy remain elusive. In this Viewpoint, we will showcase the history and importance of clozapine to neuroscience in general, as well as for the treatment of schizophrenia, and review the synthesis, pharmacology, drug metabolism, and adverse events of clozapine.

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Figures

Figure 1
Figure 1
Breakthrough medications for schizophrenia. Structures of the FGAs chlorpromazine (1) and haloperidol (2), and the SGA clozapine (3) and its major active metabolite N-desmethylclozapine (4).
Figure 2
Figure 2
Structures of closely related SGAs 5–7 to clozapine and newer TGAs 8 and 9.
Scheme 1
Scheme 1. Synthesis of Clozapine 3 Reported in Both the Primary and Patent Literature
Figure 3
Figure 3
Structures of oxidative metabolites of clozapine 3, and subsequent conjugative phase II metabolites.− The N-desmethyl metabolite 4 and the N-oxide 16 are the major metabolites, with 4 being active.
See this image and copyright information in PMC

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MeSH terms