PROTECTIVE EFFECT OF IOPHEN-5-YL)-2-[2-(N,N-DIETHYLAMINO)ETHOXY]ETHANOL HYDROCHLORIDE (T-588), A NOVEL CEREBRAL ACTIVATOR, AGAINST EXPERIMENTAL CEREBRAL ANOXIA

Effects of hiophen-5-yl)-2-[2-(NN-diethylamino)ethoxy]ethanol hydrochl oride (T-588) on normobaric hypoxia, histotoxic anoxia by KCN and comp lete ischemia by decapitation were investigated in mice. T-588 (30- 10 0 mg/kg, p.o.) showed a significant and dose-dependent prolongation of the survival time in all of the models studied. Bifemelane (100- 300 mg/kg, p.o.) was also protective against all the models. Tacrine was p rotective against hypoxia but had no effect on anoxia and ischemia. Im ipramine was protective against anoxia, but shortened the survival tim e of hypoxic mice. It had no effect on ischemia. The anti-hypoxic effe ct of T-588 was completely inhibited by pretreatment with scopolamine (I mg/kg, i.p.), while the anti-anoxic effect was partially inhibited. Its effect on the ischemia was not affected by scopolamine. Hypoxia d ecreased the cerebral contents of ATP, phosphocreatine and glucose and increased the contents of lactate in mice. T-588 had no effect on the se changes. Bifemelane prolonged pentobarbital-induced sleeping time i n mice with the doses inducing anti-anoxic action, but T-588 did not. These results suggest that the activation of the CNS cholinergic syste m is involved as one of the mechanisms for the anti-anoxic action of T -588.