[Neurotensine dipeptide analog dilept decreases the deficiency of prestimulus startle reflex inhibition: a prognostic sign of antipsychotic activity]

Abstract

The antipsychotic properties of dilept, a new drug representing substituted dipeptide based on a beta-rotational structure of the main metabolite of endogenous neuroleptic NT8-13, have been studied using the test for prestimulus inhibition (PSI) of the acoustic startle reflex in rats. It is established that dilept eliminates the PSI deficiency caused by the introduction of a noncompetitive NMDA receptor blocker ketamine, which is evidence for pronounced neuroleptic properties of the drug. Effective doses of dilept for intraperitoneal administration were 1.6, 3.2, and 6.4 mg/kg, the maximum antipsychotic effect being produced at 1.6 mg/kg. Dilept also prevented the PSI deficiency upon peroral administration in rats. In this case, the drug administration per os in the form of a tabletization mixture with poly(vinyl pyrrolidone) and lactose was more effective compared to a mixture of the parent substance with Tween-80, which can be explained by the favorable effect of additives on the bioavailability of dilept. The maximum antipsychotic effect of dilept upon oral administration was observed for a dose of 16 mg/kg. The ability of dilept to eliminate the PSI deficiency in the acoustic startle reflex test on the model of glutamate-negative psychosis in rats can be considered as a prognostic sign for the drug efficiency with respect to the negative and cognitive symptoms of schizophrenia and autism manifestations. The antidopamine activity of dilept allows us also to predict the drug efficiency with respect to the positive manifestations of schizophrenia.