Enhanced sensitivity to pentobarbital in haloperidol or pimozide treated mice and rats

The influence of intraperitoneal administration of two neuroleptic drugs, haloperidol and pimozide (2.5 and 5.0 mg/kg) on pentobarbital induced narcosis, hypothermia and lethality were investigated in mice and rats. Haloperidol and pimozide administered 10 min prior to pentobarbital sodium (60 mg/kg) injection in rats increased significantly the onset time and duration of sleep. Both neuroleptic drugs also enhanced the intensity of hypothermic response to pentobarbital (50 mg/kg). Similar enhancement of narcosis and hypothermia to pentobarbital (75 mg/kg) was observed in haloperidol and pimozide pretreated mice. Pimozide pretreatment decreased the LD50 value of pentobarbital in mice. Brain and plasma levels of pentobarbital in haloperidol and pimozide treated rats on awakening were lower than in the corresponding saline treated rats. Brain and plasma levels determined at identical time interval in saline and neuroleptic treated rats showed similar results. These data indicate that disposition of pentobarbital cannot explain its enhanced pharmacological effects in haloperidol or pimozide treated animals but the brain sensitivity to pentobarbital is altered. These studies suggest an interaction between pentobarbital and neuroleptic drugs which may have clinical relevance.