Palladium Catalyzed Cross-Coupling of Pentacyclic Phenothiazines: Novel Therapeutic Target for Positive and Negative Symptoms of Schizophrenia in Experimental Animal Models

Odin EM, Egu SA and Ochala AU

Abstract

8-Ethynylbenzene 12H-5,14-dihydroquinoxalino[2,3-a]pentacyclic phenothiazine (22) was prepared from the reaction of ethenylbenzene with stoichiometric amount of 8-chloro-12H-5,14-dihydroquinoxalino[2,3-a] pentacyclic phenothiazine according to water mediated catalyst preactivation. Structures were established by analytical and spectra data. In this study we used pharmacological methods to evaluate the effects of the novel phenothiazine compound (22) on PCP-induced behaviours. The compound was found to decrease exploratory activity in animals, which is a parameter for evaluating anxiety conditions. The novel compound also attenuated hyper-locomotion caused by PCP challenge dose and time-dependently. Treatment of animals with a combination of PCP and compound (22) significantly enhanced their social behaviour dose-dependently. The study provided evidence that the novel compound (22) mediated procognitive effects, attenuating PCP-induced deficits in Novel Object Recognition (NOR) in albino mice. The ability to reverse PCP-induced Novel Object Recognition deficits evidenced neuro-protective effects rested in the novel phenothiazine compound.

Relevant Publications in Journal of Chemical and Pharmaceutical Research