Neuroleptic binding to sigma receptors: possible involvement in neuroleptic-induced acute dystonia.
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.
Jeanjean
A P
AP
Laboratoire de Neurochimie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Laterre
E C
EC
Maloteaux
J M
JM
D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D018491:Dopamine Agonists / Q000493:pharmacokinetics; D004409:Dyskinesia, Drug-Induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics; D011813:Quinuclidinyl Benzilate / Q000493:pharmacokinetics; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D017480:Receptors, sigma / Q000187:drug effects* / Q000502:physiology; D013134:Spiperone / Q000493:pharmacokinetics
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D010880:Piperidines; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D017480:Receptors, sigma; D013134:Spiperone; D011813:Quinuclidinyl Benzilate; C026539:preclamol