Neuroleptic binding to sigma receptors: possible involvement in neuroleptic-induced acute dystonia

Biol Psychiatry. 1997 May 15;41(10):1010-9. doi: 10.1016/s0006-3223(96)00264-8.


Several antipsychotic drugs, belonging to various chemical classes, were compared for their affinity for the sigma, dopamine-D2, and muscarinic receptors. Many neuroleptic drugs were found to bind with high affinity to sigma 2 receptors, and the binding affinity was clearly different from that observed for dopamine-D2 receptors. The dopaminergic and muscarinic theories for the physiopathology of acute dystonia are not completely satisfactory. Since the sigma receptors were reported to play a role in the control of movement, the high affinity of some neuroleptics for these sites suggests their possible involvement in some side effects, such as drug-induced dystonia. There was a correlation between the clinical incidence of neuroleptic-induced acute dystonia and binding affinity of drugs for the sigma receptor, except for some drugs, with a lower incidence, displaying significant affinity for the cholinergic muscarinic receptor. Therefore, we conclude that the affinity for the sigma receptor might be involved in neuroleptic-induced acute dystonia, but this might be partially corrected by the intrinsic anticholinergic properties of the drug.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacokinetics
  • Antipsychotic Agents / toxicity*
  • Dopamine Agonists / pharmacokinetics
  • Dyskinesia, Drug-Induced / pathology
  • Dyskinesia, Drug-Induced / physiopathology*
  • Male
  • Piperidines / pharmacokinetics
  • Quinuclidinyl Benzilate / pharmacokinetics
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Dopamine D2 / physiology
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology
  • Receptors, sigma / drug effects*
  • Receptors, sigma / physiology
  • Spiperone / pharmacokinetics


  • Antipsychotic Agents
  • Dopamine Agonists
  • Piperidines
  • Receptors, Dopamine D2
  • Receptors, Muscarinic
  • Receptors, sigma
  • Spiperone
  • Quinuclidinyl Benzilate
  • preclamol