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역사The development of clozapine began in the late 1950s by researchers at the Swiss pharmaceutical company Wander. In the early 1960s, a team led by Fritz Hunziker and Jörg Schmutz synthesized the compound, a tricyclic dibenzoxazine. Clozapine's pharmacological properties differed significantly from traditional antipsychotics; it possessed potent antipsychotic activity and exhibited almost no extrapyramidal symptoms. Clozapine was approved in Europe for the treatment of schizophrenia in 1972 and in the United States in 1975. However, subsequent cases of agranulocytosis—particularly the fatal case in Finland—led to its withdrawal from the US market in 1975. Throughout the 1980s, a research team led by John Kane and Herbert Meltzer demonstrated through rigorous clinical trials that clozapine had a significant therapeutic effect on treatment-resistant schizophrenia unresponsive to traditional antipsychotics. This evidence prompted the US Food and Drug Administration (FDA) to conditionally re-approve its marketing in 1989, but only under the condition of using a rigorous blood monitoring system.

용도Clozapine is a neuroleptic, which expresses antipsychotic and sedative action. It does not cause general depression and extrapyramidal disorders. It is used for severe and chronic forms of schizophrenia, maniacal conditions, manic-depressive psychosis, psychomotor excitement, and various other psychotic conditions.

일반 설명Clozapine, 8-chloro-11-(4-methyl-1-piperazinyl)5H-dibenzo[b,e] [1,4] diazepine (Clozaril), is a yellowcrystalline powder that is only slightly soluble in water. Withthe introduction of clozapine, a different pharmacological antipsychotics.106 Unlike typical antipsychotics, clozapine is largelydevoid of EPS. The lack of EPS with this compound waspostulated to be caused by its preferential binding tomesolimbic rather than striatal DA receptors.Furthermore,clozapine was shown to exhibit potent affinity for 5-HT2Areceptors.DMCZ shows partial agonism at D2 and D3 receptors andexhibits a distinctly different pharmacological profile comparedwith clozapine and other atypical antipsychotics.Unlike clozapine, which is a potent M1 muscarinic antagonist,DMCZ is a potent M1 agonist. Agonism at muscarinicreceptors has been proposed to be useful for impaired cognitionin schizophrenia. Burnstein et al.found thatDMCZ acted as a partial agonist at DA D2 and D3 receptors.These investigators suggested that the low incidence of EPSassociated with clozapine may be caused by the partial agonismof DMCZ at D2 and D3 receptors. Thus, DMCZ maybe of interest as an atypical antipsychotic with an improvedside effect profile compared with clozapine.

정의ChEBI: A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatr c disorders like schizophrenia.