1. Academic Validation
  2. Clozapine, a fast-off-D2 antipsychotic

Clozapine, a fast-off-D2 antipsychotic

  • ACS Chem Neurosci. 2014 Jan 15;5(1):24-9. doi: 10.1021/cn400189s.
Philip Seeman 1
Affiliations

Affiliation

  • 1 Departments of Pharmacology and Psychiatry, University of Toronto , 260 Heath Street West, Unit 605, Toronto, Ontario, Canada M5P 3L6.
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.

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