title: BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats.
abstract: To clarify clinical roles of sigma receptor binding affinity of neuroleptics, neck dystonia induced by microinjection of sigma receptor ligands and neuroleptics into rat red nucleus was investigated. DTG and (+)-3-PPP, putative sigma receptor agonists, induced neck dystonia in dose-dependent and reversible manner. Haloperidol and perphenazine induced dystonia in the same way as sigma receptor agonists, whereas zotepine and (-)-sulpiride did not. The rank order of potency in induction of dystonia and sigma receptor affinity of these compounds showed positive correlation. Although BMY-14802 has a high affinity for sigma receptors, it never produced dystonia by itself. On the other hand, combined injection of BMY-14802 with DTG attenuated DTG-induced dystonia. Therefore, it is suggested that typical neuroleptics such as haloperidol act agonistic and atypical neuroleptics such as BMY-14802 act antagonistic at rubral sigma receptors in the induction of neck dystonia.
authors.affiliation: Department of Neuropsychiatry, Okayama University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: H
authors.initials: H
authors.lastname: Ujike
authors.forename: K
authors.initials: K
authors.lastname: Akiyama
authors.forename: S
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D003988:Dibenzothiepins / Q000633:toxicity; D018492:Dopamine Antagonists / Q000633:toxicity*; D065127:Dopamine D2 Receptor Antagonists; D004421:Dystonia / Q000139:chemically induced / Q000188:drug therapy*; D006146:Guanidines / Q000633:toxicity*; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D010546:Perphenazine / Q000633:toxicity; D010880:Piperidines / Q000633:toxicity*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000502:physiology; D012012:Red Nucleus / Q000187:drug effects* / Q000502:physiology; D013469:Sulpiride / Q000633:toxicity; D014103:Torticollis / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003988:Dibenzothiepins; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D006146:Guanidines; D009419:Nerve Tissue Proteins; D010880:Piperidines; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D013469:Sulpiride; C026539:preclamol; D010546:Perphenazine; D006220:Haloperidol; C050232:1,3-ditolylguanidine; C022172:zotepine