2806 Clozapine Clozapine belongs to the dibenzodiazepines, a subclass of benzodiazepines within the organic compounds. This exogenous organoheterocyclic compound has the formula C18H19ClN4 and an average molecular weight of 326.82 g/mol. At room temperature, it exists as a solid. It is found in healthcare, pharmaceuticals and veterinary products as an antipsychotic, and is also recorded in electrical and electronic equipment specifically in amplifiers. The recorded exposure route for this compound is oral. Clozapine is utilized as a second generation antipsychotic and functions as a biological application for several roles, acting as a serotonergic, dopaminergic, adrenergic, histamine, muscarinic, and GABA antagonist. Additionally, it serves as a chemical and biological inhibitor of EC 3.4.21.26 (prolyl oligopeptidase). The compound interacts with 35 recorded protein targets, including the D(4) dopamine receptor (DRD4), the D(2) dopamine receptor (DRD2), the Histamine H1 receptor (HRH1), and Neuron-specific vesicular protein calcyon (CALY). It also acts as an antagonist or positive modulator of Muscarinic acetylcholine receptors M2 (CHRM2), M3 (CHRM3), M4 (CHRM4), and M5 (CHRM5), among 14 other proteins. While the mechanism of action of Clozapine is unknown, it has been proposed that its therapeutic activity in schizophrenia is mediated through a combination of serotonin Type 2 (5HT2) and dopamine Type 2 (D2) receptor antagonism. 5786-21-0 2818 C18H19ClN4 326.129820 White powder. 183-184°C 11.8 mg/L Oral; rapid and almost complete. The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine type 2 (D₂) and serotonin type 2 (5HT₂) receptor antagonism. Atypical antipsychotic drugs such as clozapine have been proposed to block the 5HT2 and D2 receptors at therapeutic doses as evidenced by blockage in accelerating levels of growth hormone and cortisol secretion. The antipsychotic activity of clozapine is assumed to be the cause of D2 blockade while interacting with other receptors as well. With regards to mode of action in blocking dopaminergic receptors, clozapine exhibits higher affinity for D4 compared to the D2 receptor subtype. In addition, D1 antagonistic activity of clozapine enhances dopaminergic activity by increased extracellular brain dopamine concentrations specifically in the prefrontal cortex which is believed to explain its efficacy against negative symptoms generally observed in schizophrenia when using other drugs. Interestingly, clozapine has not been able to block arousal behavior which is the case when using other dopamine agonists after prolonged treatment. Interaction of clozapine with the immune system has also been found important when using this drug. Neutrophil apoptosis otherwise known as agranulocytosis was detected after administration of clopazine alone and bioactived clozapine to nitrenium ion at supratherapeutic and therapeutic levels, respectively. At supratherapeutic concentrations, clozapine can be toxic due to the drug itself or its stable metabolite products. At therapeutic levels however, the chemically reactive nitrenium ion is believed to bound to cellular protein, deplete intracellular GSH, and lead to final polymorphonuclear (PMN) and mononuclear leukocyte cytotoxicity in vitro. Agranulocytosis induced by bioactived clozapine can be inhibited by using antioxidants and genistein. PMN apoptosis is believed to be achieved by decelerating the life span of circulating cells after clozapine administration. Clozapine has also shown to interact with GABA receptors. Clozapine is able to induce release of glutamate and D-serine and decrease expression of glutamate transporters in astrocytic cell cultures with no neurons. Hepatic Route of Elimination: Approximately 50% of the administered dose is excreted in the urine and 30% in the feces. Half Life: 8 hours (range 4-12 hours) Fatal overdoses have been reported with clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 g. (L1712) No indication of carcinogenicity to humans (not listed by IARC). For use in patients with treatment-resistant schizophrenia. Clozapine may cause side effects; most are minor, although some are serious and potentially fatal. Common side effects include extreme constipation, bed-wetting, night-time drooling, muscle stiffness, sedation, tremors, orthostatic hypotension, hyperglycemia, and weight gain. The risk of developing extrapyramidal symptoms such as tardive dyskinesia is below that of typical antipsychotics; this may be due to clozapine's anticholinergic effects. Extrapyramidal symptoms may subside somewhat after a person switches from another antipsychotic to clozapine. Clozapine also carries five black box warnings, including warnings for agranulocytosis, CNS depression, leukopenia, neutropenia, seizure disorder, bone marrow suppression, dementia, hypotension, myocarditis, orthostatic hypotension (with or without syncope) and seizures. Lowering of the seizure threshold may be dose related and slow initial titration of dose may decrease the risk for precipitating seizures. Slow titration of dosing may also decrease the risk for orthostatic hypotension and other adverse cardiovascular side effects. Many male patients have experienced cessation of ejaculation during orgasm as a side effect of clozapine, though this is not documented in official drug guides. (Wikipedia) Establish and maintain an airway; ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia. There are no specific antidotes for Clozapine. (L1712) 2009-07-21T20:26:42Z 2026-05-14T16:36:36Z Clozapine C06924 3766 Clozapine DB00363 true CN1CCN(CC1)C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 C18H19ClN4 InChI=1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3 QZUDBNBUXVUHMW-UHFFFAOYSA-N 326.823 326.129824335 Exogenous Solid 3.23 HMDB14507 CHEMBL42 2716 <p>Schmutz, J. and Hunziker, F.; US. Patent 3,539,573; November 10, 1970 .</p> CHEM002181 DTXSID5022855 NS00000413 6-chloro-10-(4-methylpiperazin-1-yl)-2,9-diazatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,9,11,13-heptaene 30.870000000000005 97.35649999999998 35.76978422413783 0 4 1 15.900124965902936 7.351009067472559 1 4 3.67 -3.25 1.86e-01 g/l Organic compounds Organoheterocyclic compounds Benzodiazepines Dibenzodiazepines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 776t3gAAAAAQAAAAAwAAAAAAAAAXAAAAGgAAAIABBgBgAAAAAQMHACAAAAAD BgBgAAAAAgIGAGAAAAACAgcAKAAAAAMDBgBgAAAAAgIGAGAAAAACAgYAKAAA AAMEBwAoAAAAAwMGQCgAAAADBAZAaAAAAAMDAQZAKAAAAAMEEQAgAAAAAQZA aAAAAAMDAQZAaAAAAAMDAQZAKAAAAAMEBwBoAAAAAwIBBkAoAAAAAwQGQGgA AAADAwEGQGgAAAADAwEGQGgAAAADAwEGQGgAAAADAwEGQCgAAAADBAsAAQAB AgACAwADBAAEBQAFBgAEByAHCCgCCAkgCQpoDAoLaAwLDAALDWgMDQ5oDA4P aAwPECAQESAREmgMEhNoDBMUaAwUFWgMFRZoDAYBABYHIA8JaAwWEWgMQgQA AAAGAQYFBAMCBwgHFhEQDwkGCgsNDg8JBhITFBUWERcEAAAAAAAAABY= 2026-09-19T04:00:34Z