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{{SummarySheet}}
{{SummarySheet}}
{{SubstanceBox/Clozapine}}
{{SubstanceBox/Clozapine}}
[[File:FazaClo and Clozaril 100 mg each side by side.png|400px|thumbnail|right|FazaClo and Clozaril 100 mg tablets.]]
[[File:FazaClo and Clozaril 100 mg each side by side.png|400px|thumbnail|right|FazaClo and Clozaril 100 mg tablets.]]
'''Clozapine''', sold '''Clozaril''' and '''FazaClo''', is an [[antipsychotic|atypical antipsychotic]] substance of the tricyclic dibenzodiazepine chemical class that produces antipsychotic, hypnotic, and dulling effects when administered. It is used for treatment-resistant schizophrenia and is considered to be a "drug of last resort," reserved for when all other agents have failed.<ref> Novartis Corporation, Prescribing Guide For Clozapine (https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf)</ref> It is also used for schizoaffective disorder, a similar condition. FazaClo is an orally disintegrating tablet. <ref>Jazz Pharmaceuticals (2017) FazaClo Highlights of Prescribing Information</ref>
'''Clozapine''', sold '''Clozaril''' and '''FazaClo''', is an [[antipsychotic|atypical antipsychotic]] substance of the tricyclic dibenzodiazepine chemical class that produces antipsychotic, hypnotic, and dulling effects when administered. It is used for treatment-resistant schizophrenia and is considered to be a "drug of last resort," reserved for when all other agents have failed.<ref> Novartis Corporation, Prescribing Guide For Clozapine (https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019758s062lbl.pdf)</ref> It is also used for schizoaffective disorder, a similar condition. FazaClo is an orally disintegrating tablet. <ref>Jazz Pharmaceuticals (2017) FazaClo Highlights of Prescribing Information</ref>
Clozapine may also be used to help reduce the risk of suicidal tendencies in people with schizophrenia or other disorders that can be similar, such as acute delirium, bipolar disorder, and extreme cases of anxiety.{{citation needed}} However, it is only approved for use (on-label) in treatment-resistant schizophrenia. Clozapine was first synthesized in 1958 by Wander AG, a Swiss pharmaceutical company, based on the structure of the tricyclic antidepressant imipramine.
Clozapine may also be used to help reduce the risk of suicidal tendencies in people with schizophrenia or other disorders that can be similar, such as acute delirium, bipolar disorder, and extreme cases of anxiety.{{citation needed}} However, it is only approved for use (on-label) in treatment-resistant schizophrenia. Clozapine was first synthesized in 1958 by Wander AG, a Swiss pharmaceutical company, based on the structure of the tricyclic antidepressant imipramine.
==Chemistry==
==Chemistry==
{{chemistry}}
{{chemistry}}
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==Pharmacology==
==Pharmacology==
Clozapine is classified as and was the first atypical antipsychotic agent. It binds to several types of central nervous system receptors and displays a unique pharmacological profile. It is a [[serotonin]] antagonist, with strong binding to the 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> receptor subtypes. Clozapine has clinically significant anticholinergic activity, and this activity may make clozapine one of the few, if any other antipsychotic agents to have very low induction rates of tardive dyskinesia.<ref>Lieberman, J., Johns, C., Cooper, T., Pollack, S., & Kane, J. (1989). Clozapine pharmacology and tardive dyskinesia. Psychopharmacology, 99(1), S54-S59.</ref>
Clozapine is classified as and was the first atypical [[antipsychotic]] agent. It binds to several types of central nervous system receptors and displays a unique pharmacological profile. It is a [[serotonin]] [[antagonist]], with strong binding to the 5-HT<sub>2A</sub> and 5-HT<sub>2C</sub> [[receptor]] subtypes.<ref name="Clozapine">Clozapine (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/mesh/68003024</ref> Clozapine has clinically significant anticholinergic activity, and this activity may make clozapine one of the few, if any other antipsychotic agents to have very low induction rates of tardive dyskinesia.<ref>Lieberman, J., Johns, C., Cooper, T., Pollack, S., & Kane, J. (1989). Clozapine pharmacology and tardive dyskinesia. Psychopharmacology, 99(1), S54-S59.</ref>
It also displays a strong affinity as an antagonist to several [[dopamine|dopaminergic]] receptors, but shows only weak antagonism at the dopamine D2 receptor, which is commonly thought to modulate neuroleptic activity.
It also displays a strong affinity as an [[antagonist]] to several [[dopamine|dopaminergic]] receptors, but shows only weak antagonism at the [[dopamine]] D2 [[receptor]], which is commonly thought to modulate neuroleptic activity.<ref name="Clozapine"/>
[https://en.wikipedia.org/wiki/Agranulocytosis Agranulocytosis] (severely low white blood cell count) is a major adverse effect associated with the administration of this agent.<ref>Baldessarini, R. J., & Frankenburg, F. R. (1991). Clozapine: a novel antipsychotic agent. New England Journal of Medicine, 324(11), 746-754.</ref><ref>Smits, R. A., Lim, H. D., Stegink, B., Bakker, R. A., de Esch, I. J., & Leurs, R. (2006). Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. Journal of medicinal chemistry, 49(15), 4512-4516.</ref>
[https://en.wikipedia.org/wiki/Agranulocytosis Agranulocytosis] (severely low white blood cell count) is a major adverse effect associated with the administration of this agent.<ref>Baldessarini, R. J., & Frankenburg, F. R. (1991). Clozapine: a novel antipsychotic agent. New England Journal of Medicine, 324(11), 746-754.</ref><ref>Smits, R. A., Lim, H. D., Stegink, B., Bakker, R. A., de Esch, I. J., & Leurs, R. (2006). Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. Journal of medicinal chemistry, 49(15), 4512-4516.</ref>
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===Experience reports===
===Experience reports===
Anecdotal reports which describe the effects of this compound within our [[experience index]] include:
There are currently {{#ask:[[Category:SUBSTANCE]][[Category:Experience]] | format=count}} experience reports which describe the effects of this substance in our [[experience index]].
Clozapine can also cause NMS, or neuroleptic malignant syndrome. This reaction is rare, but serious and includes dysfunctions such as muscle rigidity, hyperthermia, paleness, psychomotor agitation, respiratory distress (tachypnea), among others.{{citation needed}}
Clozapine can also cause NMS, or neuroleptic malignant syndrome. This reaction is rare, but serious and includes dysfunctions such as muscle rigidity, hyperthermia, paleness, psychomotor agitation, respiratory distress (tachypnea), among others.{{citation needed}}
==Legality==
==Legal status==
{{LegalStub}}
{{LegalStub}}
*'''United States:''' Clozapine is not a controlled substance, but is a prescription-only medicine. Bloodwork for a condition called agranulocytosis is often done for safety before prescribing and sometimes while on the medication.
*'''United States:''' Clozapine is not a controlled substance, but is a prescription-only medicine. Bloodwork for a condition called agranulocytosis is often done for safety before prescribing and sometimes while on the medication.
[[Category:Psychoactive substance]][[Category:Articles in talk page]][[Category:Proofread]][[Category:Approval]]
[[Category:Proofread]]
Latest revision as of 22:12, 13 November 2020
This article is in the 'Talk' namespace because it is an unfinished draft. This section is used to host drafts for unpublished articles as well as discussions for published ones. If you'd like to use this area to discuss this draft, please do so in the 'Discussion' section at the very bottom of the page. This notice will be removed once this draft has been approved for publication by an administrator.
Please help by contributing so that this article can be published. It would be appreciated if the substancebox was verified and the references at the bottom were located and formatted. --Corticosteroid (talk) 02:56, 5 October 2017 (CEST)
It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks. It may also not meet PW style and grammar standards.
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
FazaClo and Clozaril 100 mg tablets.
Clozapine, sold Clozaril and FazaClo, is an atypical antipsychotic substance of the tricyclic dibenzodiazepine chemical class that produces antipsychotic, hypnotic, and dulling effects when administered. It is used for treatment-resistant schizophrenia and is considered to be a "drug of last resort," reserved for when all other agents have failed.[1] It is also used for schizoaffective disorder, a similar condition. FazaClo is an orally disintegrating tablet. [2]
Clozapine may also be used to help reduce the risk of suicidal tendencies in people with schizophrenia or other disorders that can be similar, such as acute delirium, bipolar disorder, and extreme cases of anxiety.[citation needed] However, it is only approved for use (on-label) in treatment-resistant schizophrenia. Clozapine was first synthesized in 1958 by Wander AG, a Swiss pharmaceutical company, based on the structure of the tricyclic antidepressant imipramine.
Clozapine is a tricyclic dibenzodiazepine. Its main structure is of two benzene rings fused to a 1,3-diazepine ring, one benzene being chlorinated. [3][4]
Pharmacology
Clozapine is classified as and was the first atypical antipsychotic agent. It binds to several types of central nervous system receptors and displays a unique pharmacological profile. It is a serotoninantagonist, with strong binding to the 5-HT2A and 5-HT2Creceptor subtypes.[5] Clozapine has clinically significant anticholinergic activity, and this activity may make clozapine one of the few, if any other antipsychotic agents to have very low induction rates of tardive dyskinesia.[6]
It also displays a strong affinity as an antagonist to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, which is commonly thought to modulate neuroleptic activity.[5]
Agranulocytosis (severely low white blood cell count) is a major adverse effect associated with the administration of this agent.[7][8]
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Anxiety suppression & Anxiety - At theraputic doses, clozapine suppresses anxiety, but at higher dosages it may cause anxiety due to its anticholinergic activity.
Hallucinations - These only occur in very high doses and as a result of clozapine's anticholinergic activity.
Paradoxical effects
Paradoxical reactions to antipsychotics such as worsened psychosis, violent behavior, loss of impulse control, irritability, and suicidal behavior sometimes occur (although they are rare in the general population).[citation needed]
Experience reports
There are currently 0 experience reports which describe the effects of this substance in our experience index.
Clozapine is associated with a rare but potentially fatal effect called agranulocytosis (dangerously low white blood cell count).[10] Therefore, lower doses and self-monitoring for this condition are encouraged if taken outside of supervised medical context.
Clozapine can also cause NMS, or neuroleptic malignant syndrome. This reaction is rare, but serious and includes dysfunctions such as muscle rigidity, hyperthermia, paleness, psychomotor agitation, respiratory distress (tachypnea), among others.[citation needed]
As such, it may contain incomplete or wrong information. You can help by expanding it.
United States: Clozapine is not a controlled substance, but is a prescription-only medicine. Bloodwork for a condition called agranulocytosis is often done for safety before prescribing and sometimes while on the medication.
Australia: Clozapine is a schedule four substance, meaning it is a prescription-only medicine.
↑Jazz Pharmaceuticals (2017) FazaClo Highlights of Prescribing Information
↑Baldessarini, R. J., & Frankenburg, F. R. (1991). Clozapine: a novel antipsychotic agent. New England Journal of Medicine, 324(11), 746-754.
↑Smits, R. A., Lim, H. D., Stegink, B., Bakker, R. A., de Esch, I. J., & Leurs, R. (2006). Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. Journal of medicinal chemistry, 49(15), 4512-4516.
↑Lieberman, J., Johns, C., Cooper, T., Pollack, S., & Kane, J. (1989). Clozapine pharmacology and tardive dyskinesia. Psychopharmacology, 99(1), S54-S59.
↑Baldessarini, R. J., & Frankenburg, F. R. (1991). Clozapine: a novel antipsychotic agent. New England Journal of Medicine, 324(11), 746-754.
↑Smits, R. A., Lim, H. D., Stegink, B., Bakker, R. A., de Esch, I. J., & Leurs, R. (2006). Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. Journal of medicinal chemistry, 49(15), 4512-4516.
↑Chengappa, K. R., Pollock, B. G., Parepally, H., Levine, J., Kirshner, M. A., Brar, J. S., & Zoretich, R. A. (2000). Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine. Journal of clinical psychopharmacology, 20(3), 311-316.
↑Mebanga Ojong and Shari N. Allen (2013) Management and prevention of agranulocytosis in patients receiving clozapine. Mental Health Clinician: September 2013, Vol. 3, No. 3, pp. 139-143. https://doi.org/10.9740/mhc.n166825
