Clozapine, a fast-off-D2 antipsychotic.
Identifieur interne : 000778 ( PubMed/Checkpoint ); précédent : 000777; suivant : 000779Clozapine, a fast-off-D2 antipsychotic.
Auteurs : Philip Seeman [Canada]Source :
- ACS chemical neuroscience [ 1948-7193 ] ; 2014.
English descriptors
- KwdEn :
- Animals, Antipsychotic Agents (chemistry), Antipsychotic Agents (pharmacology), Antipsychotic Agents (therapeutic use), Clozapine (chemistry), Clozapine (pharmacology), Clozapine (therapeutic use), Corpus Striatum (drug effects), Corpus Striatum (metabolism), Humans, Mental Disorders (drug therapy), Protein Binding (drug effects), Receptors, Dopamine D2 (metabolism).
- MESH :
- chemical , chemistry : Antipsychotic Agents, Clozapine.
- chemical , metabolism : Receptors, Dopamine D2.
- chemical , pharmacology : Antipsychotic Agents, Clozapine.
- chemical , therapeutic use : Antipsychotic Agents, Clozapine.
- drug effects : Corpus Striatum, Protein Binding.
- drug therapy : Mental Disorders.
- metabolism : Corpus Striatum.
- Animals, Humans.
Abstract
Ever since clozapine was first synthesized and tested, it showed the unique property of having antipsychotic action but no Parkinson-like motor side effects. The antipsychotic basis of clozapine is to transiently occupy dopamine D2 receptors in the human striatum, in contrast to haloperidol and chlorpromazine, which have a prolonged occupation of D2 receptors. The chemical structure of clozapine facilitates a relatively rapid dissociation from D2 receptors. After short-term occupation of D2 receptors, peak neural activity raises synaptic dopamine, which then displaces clozapine. While clozapine also occupies other types of receptors, they may not have a significant role in preventing parkinsonism. Clozapine's transient occupation of D2 receptors permits patients to move easily and comfortably.
DOI: 10.1021/cn400189s
PubMed: 24219174
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:24219174Le document en format XML
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The antipsychotic basis of clozapine is to transiently occupy dopamine D2 receptors in the human striatum, in contrast to haloperidol and chlorpromazine, which have a prolonged occupation of D2 receptors. The chemical structure of clozapine facilitates a relatively rapid dissociation from D2 receptors. After short-term occupation of D2 receptors, peak neural activity raises synaptic dopamine, which then displaces clozapine. While clozapine also occupies other types of receptors, they may not have a significant role in preventing parkinsonism. Clozapine's transient occupation of D2 receptors permits patients to move easily and comfortably.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24219174</PMID><DateCreated><Year>2014</Year><Month>01</Month><Day>16</Day></DateCreated><DateCompleted><Year>2014</Year><Month>09</Month><Day>09</Day></DateCompleted><DateRevised><Year>2015</Year><Month>04</Month><Day>22</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1948-7193</ISSN><JournalIssue CitedMedium="Internet"><Volume>5</Volume><Issue>1</Issue><PubDate><Year>2014</Year><Month>Jan</Month><Day>15</Day></PubDate></JournalIssue><Title>ACS chemical neuroscience</Title><ISOAbbreviation>ACS Chem Neurosci</ISOAbbreviation></Journal><ArticleTitle>Clozapine, a fast-off-D2 antipsychotic.</ArticleTitle><Pagination><MedlinePgn>24-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/cn400189s</ELocationID><Abstract><AbstractText>Ever since clozapine was first synthesized and tested, it showed the unique property of having antipsychotic action but no Parkinson-like motor side effects. The antipsychotic basis of clozapine is to transiently occupy dopamine D2 receptors in the human striatum, in contrast to haloperidol and chlorpromazine, which have a prolonged occupation of D2 receptors. The chemical structure of clozapine facilitates a relatively rapid dissociation from D2 receptors. After short-term occupation of D2 receptors, peak neural activity raises synaptic dopamine, which then displaces clozapine. While clozapine also occupies other types of receptors, they may not have a significant role in preventing parkinsonism. Clozapine's transient occupation of D2 receptors permits patients to move easily and comfortably.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Seeman</LastName><ForeName>Philip</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Departments of Pharmacology and Psychiatry, University of Toronto , 260 Heath Street West, Unit 605, Toronto, Ontario, Canada M5P 3L6.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>11</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>ACS Chem Neurosci</MedlineTA><NlmUniqueID>101525337</NlmUniqueID><ISSNLinking>1948-7193</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014150">Antipsychotic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017448">Receptors, Dopamine D2</NameOfSubstance></Chemical><Chemical><RegistryNumber>J60AR2IKIC</RegistryNumber><NameOfSubstance UI="D003024">Clozapine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Am J Psychiatry. 1999 Nov;156(11):1686-96</RefSource><PMID Version="1">10553730</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>ACS Chem Neurosci. 2013 Jul 17;4(7):1018-25</RefSource><PMID Version="1">24047509</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Arch Gen Psychiatry. 2000 Jun;57(6):553-9</RefSource><PMID 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Version="1">10619175</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014150" MajorTopicYN="N">Antipsychotic Agents</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003024" MajorTopicYN="N">Clozapine</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003342" MajorTopicYN="N">Corpus Striatum</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001523" MajorTopicYN="N">Mental Disorders</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017448" MajorTopicYN="N">Receptors, Dopamine D2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC3894721</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2013</Year><Month>11</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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