dihydroergotoxine and pantogab

Effects of Y-8894 on learning and memory were studied using a radial maze task in intact and scopolamine-induced amnesic mice. The following results were obtained: 1) Repeated administration of Y-8894 (1, 2.5 and 5 mg/kg, i.p.) significantly increased the number of initial correct responses (ICR) in the training session in intact mice, facilitating the learning of the maze task. Dihydroergotoxine (5 mg/kg, i.p.) significantly facilitated the learning of this task in the initial stage of the training session, but non-specifically inhibited the performance in the late stage of training. Ca-hopantenate did not modify the learning of this task. 2) A single administration of Y-8894 (2.5 or 5 mg/kg, i.p.) showed an antagonistic effect on scopolamine (1 mg/kg, s.c.)-induced amnesic mice. Dihydroergotoxine (5 mg/kg, i.p.) and Ca-hopantenate (500 mg/kg, i.p.) also significantly antagonized the ICR-decreasing effect of scopolamine. These results suggest that Y-8894 has an ameliorative and/or facilitative effect on learning and memory in the radial maze task, and Y-8894 is more potent than dihydroergotoxine and Ca-hopantenate.

Topics: Amnesia; Animals; Dihydroergotoxine; gamma-Aminobutyric Acid; Learning; Memory; Mice; Morpholines; Pantothenic Acid; Scopolamine

The effect of Y-8894 (+/-) 2-[[o-(2-thenyl)phenoxy]methyl] morpholine maleate, which has been shown to improve experimentally induced learning and memory deficits, on cerebral monoamine uptake and turnover was studied in the mouse. The following results were obtained: 1) It inhibited in vitro norepinephrine (NE) uptake to the mouse cerebral synaptosomal fractions about 800 and 1250 times more potently than it did those of dopamine (DA) and serotonin (5-HT), respectively. 2) It dose-dependently inhibited in vivo NE uptake, but not DA or 5-HT uptake. 3) It reduced the accumulation of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), increased that of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and had no effect on that of the DA metabolite, homovanillic acid (HVA). These effects were compared with those of imipramine, calcium hopantenate (Ca-hopantenate) and dihydroergotoxine. Y-8894 appeared to act by stimulating the noradrenergic receptor, and it acts to a lesser extent by blocking the serotonergic receptor in the brain.

Topics: Animals; Biogenic Amines; Brain; Central Nervous System Stimulants; Dihydroergotoxine; Dopamine; gamma-Aminobutyric Acid; Homovanillic Acid; Hydroxyindoleacetic Acid; Imipramine; Male; Methoxyhydroxyphenylglycol; Mice; Morpholines; Norepinephrine; Pantothenic Acid; Serotonin

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 anti-anoxic effect of sufoxazine was investigated in various cerebral anoxia models with mice, in comparison with those of various cerebroactive drugs. Sufoxazine reduced dose-dependently the duration of coma induced by a sublethal dose of KCN (1.8 mg/kg, i.v.), significantly stimulating recovery from the coma at 5 mg/kg, i.p. and 30 mg/kg, p.o. It also protected against a lethal dose of KCN (2.5 mg/kg, i.v.). Sufoxazine prolonged the survival time of mice subjected to hypobaric and normobaric hypoxia. Dihydroergotoxin and ifenprodil gave similar protection in the KCN-induced anoxia models, but produced adverse effects in the hypoxia models. Calcium hopantenate exerted similar but weak protection only at a dose as high as 300 mg/kg, i.p. These findings suggest that sufoxazine has an anti-anoxic action superior to those of the other cerebroactive drugs used.

Topics: Animals; Atmospheric Pressure; Coma; Dihydroergotoxine; Drug Therapy, Combination; gamma-Aminobutyric Acid; Hypoxia, Brain; Mice; Morpholines; Pantothenic Acid; Physostigmine; Piperidines; Potassium Cyanide