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Clozapine was the first true breakthrough in schizophrenia treatment since the discovery of chlorpromazine ineffectively treating positive, negative, and some cognitive symptoms, as well as possessing unprecedented efficacy in treatment-resistant patients. 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. However, the FGAs led to extrapyramidal side effects EPS via their actions at D 2 muscle rigidity, tremors, Parkinsonian-like symptomswhich resulted in poor patient compliance. As will be detailed later in this Viewpoint, 3 is a preeminent example of serendipitous polypharmacology.

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