Clozapine, a fast-off-D2 antipsychotic

ACS Chem Neurosci. 2014 Jan 15;5(1):24-9. doi: 10.1021/cn400189s. Epub 2013 Nov 18.


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.

Publication types

  • Review

MeSH terms

  • 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*


  • Antipsychotic Agents
  • Receptors, Dopamine D2
  • Clozapine