cinepazide and Hypoxia

Effects of indeloxazine hydrochloride [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054] on anoxia were examined. Indeloxazine significantly prolonged survival time of mice subjected to anoxia and improved anoxia-induced impairment of the passive and active avoidance learnings in rats. Indeloxazine at doses inducing anti-anoxic actions showed no effect on cerebral blood flow in cats and pentobarbital sleeping time in mice. Therefore, anti-anoxic actions of indeloxazine are not attributable to cerebral vasodilative or central depressant activities. Calcium hopantenate (cerebral metabolic enhancer) also showed anti-anoxic actions, whereas neither viloxazine, amitriptyline (antidepressant) nor dihydroergotoxine (cerebral vasodilator) showed any effect on anoxia. These results suggest that indeloxazine possesses anti-anoxic activities similar to calcium hopantenate. The mode of anti-anoxic actions of indeloxazine is also discussed.

Topics: Amitriptyline; Animals; Avoidance Learning; Cerebrovascular Circulation; Dihydroergotoxine; Female; gamma-Aminobutyric Acid; Hypoxia; Male; Mice; Mice, Inbred ICR; Morpholines; Pantothenic Acid; Piperazines; Rats; Rats, Inbred Strains; Sleep; Time Factors; Viloxazine

The effects of cinepazide, a vasodilator, on the content, biosynthesis and turnover of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) in the rat brain were examined under room air and hypoxia (10% O2, 90% N2). Under room air, cinepazide had no significant effects on the content of NA, DA, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA), the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) after central decarboxylase inhibition, and the depletion of NA, DA and 5-HT after synthesis inhibition. After 2 hr-exposure to hypoxia, the content of NA, 5-HT and 5-HIAA was decreased, whereas the content of DA was unchanged. The accumulation of DOPA and 5-HTP was decreased. The depletion of DA and 5-HT was inhibited by hypoxia, whereas the depletion of NA was unaffected. Under hypoxic conditions, cinepazide had no effects on the content of NA, DA and 5-HT, the accumulation of DOPA and 5-HTP, and the depletion of NA and DA, whereas cinepazide increased both the rate of 5-HT depletion and the content of 5-HIAA. The present data suggest that cinepazide selectively stimulates the functional activities of 5-HT neurons in the brain, which are depressed by hypoxia.

Topics: 5-Hydroxytryptophan; Animals; Brain; Dihydroxyphenylalanine; Dopamine; Hydroxyindoleacetic Acid; Hydroxylation; Hypoxia; Kinetics; Male; Norepinephrine; Piperazines; Rats; Serotonin; Tryptophan; Tyrosine; Vasodilator Agents