Protective effect of R(-)-1-(benzo[b]thiophen-5-yl)- 2-[2-(N,N-diethylamino)ethoxy]ethanol hydrochloride (T-588), a novel cerebral activator, against experimental cerebral anoxia.
Effects of R(-)-1-(benzo[b]thiophen-5-yl)-2-[2- (N,N-diethylamino)ethoxy]ethanol hydrochloride (T-588) on normobaric hypoxia, histotoxic anoxia by KCN and complete ischemia by decapitation were investigated in mice. T-588 (30-100 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 protective against hypoxia but had no effect on anoxia and ischemia. Imipramine was protective against anoxia, but shortened the survival time of hypoxic mice. It had no effect on ischemia. The anti-hypoxic effect of T-588 was completely inhibited by pretreatment with scopolamine (1 mg/kg, i.p.), while the anti-anoxic effect was partially inhibited. Its effect on the ischemia was not affected by scopolamine. Hypoxia decreased the cerebral contents of ATP, phosphocreatine and glucose and increased the contents of lactate in mice. T-588 had no effect on these changes. Bifemelane prolonged pentobarbital-induced sleeping time in mice with the doses inducing anti-anoxic action, but T-588 did not. These results suggest that the activation of the CNS cholinergic system is involved as one of the mechanisms for the anti-anoxic action of T-588.
Ono
S
S
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Kitamura
K
K
Maekawa
M
M
Hirata
K
K
Ano
M
M
Ukai
W
W
Yamafuji
T
T
Narita
H
H
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D004048:Diethylamines / Q000627:therapeutic use*; D004734:Energy Metabolism / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D002534:Hypoxia, Brain / Q000503:physiopathology / Q000517:prevention & control*; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010424:Pentobarbital / Q000494:pharmacology; D011190:Potassium Cyanide / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013619:Tacrine / Q000494:pharmacology; D013876:Thiophenes / Q000627:therapeutic use*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D004048:Diethylamines; D013876:Thiophenes; C082372:T 588; D013619:Tacrine; D012601:Scopolamine; D010424:Pentobarbital; D011190:Potassium Cyanide; D007099:Imipramine; C031906:bifemelane