BMY-14802 reversed the σ receptor agonist-induced neck dystonia in rats

Summary To clarify clinical roles of s receptor binding affinity of neuroleptics, neck dystonia induced by microinjection of s receptor ligands and neuroleptics into rat red nucleus was investigated. DTG and (+)-3-PPP, putative s receptor agonists, induced neck dystonia in dose-dependent and reversible manner. Haloperidol and perphenazine induced dystonia in the same way as s receptor agonists, whereas zotepine and (-)-sulpiride did not. The rank order of potency in induction of dystonia and s receptor affinity of these compounds showed positive correlation. Although BMY-14802 has a high affinity for s 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 s receptors in the induction of neck dystonia.