ubiquinone and indeloxazine

Topics: Aged; Antidepressive Agents; Benzoquinones; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Dementia; Humans; Middle Aged; Morpholines; Ubiquinone; Vasodilator Agents

Bifemelane hydrochloride (bifemelane), idebenone and indeloxazine hydrochloride (indeloxazine) are used clinically to reduce apathy and other emotional disturbances in patients with cerebrovascular disease. In gerbil brains, ischemia affects many monoaminergic neurotransmitters and their metabolites. In the present study, the effects of treatment with bifemelane, idebenone and indeloxazine on ischemia-induced changes in monoamines and their metabolites were studied in ischemic gerbil brains. Although these drugs had no effect on the monoaminergic neurotransmitters or their metabolites in sham-operated animals, in the ischemic brains both dopamine and serotonin turnovers were abnormal after idebenone or indeloxazine treatment. Bifemelane, in contrast, tended to correct the ischemia-induced changes in the dopaminergic and serotonergic systems in the cerebral cortex, hippocampus and thalamus + midbrain. From the present results and those in previous reports, we conclude that bifemelane is more appropriate than idebenone or indeloxazine as a treatment for the ischemia-induced changes in monoaminergic neurotransmitter systems.

Topics: Animals; Benzhydryl Compounds; Benzoquinones; Biogenic Monoamines; Brain Chemistry; Brain Ischemia; Dopamine; Gerbillinae; Hydroxyindoleacetic Acid; Morpholines; Nerve Tissue Proteins; Norepinephrine; Serotonin; Ubiquinone

Age-related changes in the acquisition and retention of memory based on the step-through active avoidance response were studied in rats and the effects of cholinergic drugs and cerebral metabolic activators on memory impairment in old rats were also tested. Six- and 12-month-old rats showed lower rates of acquisition of the active avoidance response than did 2-month-old rats. In addition, the retention of the active avoidance response in 6- and 12-month-old rats diminished rather rapidly compared with that observed in 2-month-old rats. Intraventricular injection of acetylcholine at doses of 20 and 50 ng caused a significant improvement of memory impairment in old rats. Physostigmine and arecoline also caused a significant ameliorating effect at doses of 0.02 and 0.05 mg/kg i.p. and 0.2 and 0.5 mg/kg i.p., respectively. Hopantenate calcium (100 mg/kg, p.o.), idebenone (20 and 50 mg/kg, i.p.), indeloxazine (50 mg/kg, p.o.) and DM-9384 (30 mg/kg, p.o.) also proved useful to improve memory impairment in old rats.

Topics: Acetylcholine; Aging; Animals; Benzoquinones; Brain; Central Nervous System Agents; gamma-Aminobutyric Acid; Learning; Male; Memory Disorders; Morpholines; Pantothenic Acid; Parasympathomimetics; Pyrrolidinones; Rats; Rats, Inbred Strains; Ubiquinone

The ameliorating effects of idebenone and indeloxazine hydrochloride on the impairment of memory and learning were studied in cerebral embolized rats. The embolized rats had impaired memory and learning ability in the radial maze task; these were demonstrated by a decrease in correct responses and an increase in total errors. In particular, the rats showed severe impairment of working memory, as shown by a marked increase in the numbers of re-entries into the arm that had been already visited. Idebenone (30 mg/kg, p.o.) exerted marked ameliorating effects on the impairment in the embolized rats: the drug significantly increased the correct responses and decreased the errors. Indeloxazine hydrochloride also improved the memory impairment in the embolized rats, as shown by a reduction of the errors. The ameliorating effects of these drugs may be due mainly to improvement of hypofunctions of the central nervous system. These results confirm that idebenone and indeloxazine hydrochloride may have ameliorating actions on impairment of memory and learning induced by brain hypofunction, and they suggest that the action of idebenone is more potent than that of indeloxazine hydrochloride.

Topics: Animals; Antidepressive Agents; Benzoquinones; Intracranial Embolism and Thrombosis; Learning Disabilities; Male; Memory Disorders; Morpholines; Quinones; Rats; Rats, Inbred Strains; Ubiquinone

Effects of bifemelane hydrochloride, idebenone and indeloxazin hydrochloride on ischemia-induced decrease in acetylcholine (ACh) levels were studied in gerbils. Among these three drugs, only bifemelane hydrochloride significantly inhibited the decrease in ACh concentration in the cerebral cortex, hippocampus and striatum of ischemic gerbils. This suggests that bifemelane hydrochloride has an anti-ischemic action and beneficial effects on various symptoms induced by ischemia.

Topics: Acetylcholine; Animals; Benzhydryl Compounds; Benzoquinones; Brain Chemistry; Brain Ischemia; Cerebral Cortex; Corpus Striatum; Gerbillinae; Hippocampus; Humans; Infant, Newborn; Morpholines; Quinones; Ubiquinone

The effects of idebenone and various nootropic drugs on lipid peroxidation in rat brain homogenate were examined. Idebenone inhibited lipoperoxide (LPO) production in brain homogenate in a concentration-dependent manner, with an IC50 of 38 microM. The inhibition was strongly enhanced (about 100-fold) by adding succinate, a substrate in the mitochondrial respiration. The optimal concentration of succinate was 0.5 mM. Inhibition of lipid peroxidation in brain homogenate by various nootropic drugs in the presence or absence of succinate was then examined. Drugs added to the brain homogenate at 100 microM in the absence of succinate inhibited LPO production in the order: idebenone greater than vinpocetine greater than bifemelane greater than indeloxazine greater than calcium hopantenate. However, when the drugs were added at 1 microM in the presence of succinate, only idebenone demonstrated inhibition. These results suggest that although almost all of the drugs tested inhibit lipid peroxidation in brain homogenate, only idebenone is activated by succinate, the other drugs being insensitive to this compound.

Topics: Animals; Benzhydryl Compounds; Benzoquinones; Brain; Depression, Chemical; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; In Vitro Techniques; Lipid Peroxides; Male; Morpholines; Pantothenic Acid; Quinones; Rats; Rats, Inbred Strains; Succinates; Ubiquinone; Vinca Alkaloids