[Anti-anoxic effect of 4-(o-benzlphenoxy)-N-methylbutylamine hydrochloride (MCI-2016)].
Anti-anoxic effects of MCI-2016 were compared with those of drugs for cerebrovascular diseases, tricyclic antidepressants and physostigmine in mice. Minimal effective doses of MCI-2016 which significantly increased the survival time or gasping duration were 12.5 mg/kg, p.o. for hypoxia, 50 mg/kg, p.o. for KCN-induced anoxia, and 100 mg/kg, p.o. for decapitation-induced gasping. As a whole, these effects of MCI-2016 were superior to those of reference drugs for cerebrovascular diseases. MCI-2016 was also shown to be effective under a consecutive administration schedule. In marked contrast to the effect of MCI-2016, tricyclic antidepressants significantly shortened the survival time under hypoxia. Considering that atropine shortened and physostigmine markedly increased the survival time under hypoxia, involvement of anti-cholinergic action may be postulated for the shortening effect of tricyclic antidepressants. The anti-hypoxic effect of MCI-2016 as well as physostigmine was diminished by atropine treatment. Furthermore, MCI-2016 exhibited a combination effect with physostigmine at optimal doses. Although the influence of norepinephrine uptake inhibitory action on the hypoxic condition are not clear in the present study, these results may suggest that activation of CNS cholinergic system is involved as one of the causative mechanisms for anti-anoxic effect of MCI-2016.
D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001285:Atropine / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D000860:Hypoxia / Q000188:drug therapy*; D008297:Male; D051379:Mice; D010830:Physostigmine / Q000494:pharmacology
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D001559:Benzhydryl Compounds; D001285:Atropine; D010830:Physostigmine; C031906:bifemelane