Clozapine, a fast-off-D2 antipsychotic.
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.
Departments of Pharmacology and Psychiatry, University of Toronto , 260 Heath Street West, Unit 605, Toronto, Ontario, Canada M5P 3L6.
Philip
P
Seeman
D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D003024:Clozapine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*; D011485:Protein Binding / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D003024:Clozapine