NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats, dogs and monkeys.

NE-100, a drug being considered for schizophrenia, had no effect on conditioned avoidance responses in rats but attenuated PCP-induced impairment of avoidance inhibition. In rhesus monkeys, NE-100 partially overcame PCP-induced ataxia or decreased attention. In dogs, NE-100 blocked PCP-induced head-weaving behavior or ataxia. PCP increased beta-2 and decreased delta relative power in cortical ECoG activity in dogs; NE-100 alone showed no significant change in these measures but blocked the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effects of PCP in experimental animals.

Study at a glance

Abstract

Phencyclidine (PCP)-induced psychosis is a useful animal model for studies on schizophrenia. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]- ethylamine monohydrochloride (NE-100) had no effect on conditioned avoidance responses (CAR) in rats, whereas, the PCP-induced impairment of avoidance inhibition was attenuated by NE-100. The PCP-induced ataxia or decreased attention in rhesus monkeys was to some extent overcome by NE-100. In dogs, PCP-induced either head-weaving behavior or ataxia, effects which were blocked by NE-100. Administration of PCP led to an increase in beta-2 and a decrease in delta relative power (RP) activity in cortical background spectral electroencephalographics (ECoG) in dogs. While NE-100 in itself showed no significant change in beta-2 and delta RP, NE-100 did block the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effect of PCP in experimental animals. This drug is being considered as a therapeutic for the treatment of patients in the schizophrenia.