sm-346 and Ischemic-Attack--Transient

The effect of nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA conjugates with arachidonic acid and docosahexaenoyl dopamine on the cerebral circulation has been studied in intact rats and those with global transient cerebral ischemia, experimental myocardial infarction, and combined vascular pathology of brain and heart. The most pronounced vasodilation activity in rats with global transient cerebral ischemia is exhibited by nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA-containing lipid derivatives. This effect of all these drugs (except for nimodipine) is not manifested on the background of GABA receptor blocker bicuculline. In rats with experimental myocardial infarction and combined vascular pathology of brain and heart not all of the compounds mentioned acbove with GABA-ergic mechanism of action stimulate the cerebral blood flow. Thus, both similarity and differences in cerebrovascular effects of these compounds have been found, which depend on the initial state of organism and the vascular pathology of brain and/or heart. The obtained results show good prospects for this direction of research.

Topics: Adamantane; Animals; Animals, Outbred Strains; Benzimidazoles; Bicuculline; Cerebral Cortex; Dopamine; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Ischemic Attack, Transient; Male; Melatonin; Morpholines; Myocardial Infarction; Nimodipine; Picolines; Rats; Receptors, GABA; Structure-Activity Relationship; Vasodilation; Vasodilator Agents

Anxiolytic agent afobazole (10 mg/kg intraperitoneally) 24 h after ischemia restores impaired balance of excitatory and inhibitory amino acids in the striatum of mongrel rats, normalizes their content to control levels, and activates endogenous taurine-dependent system of neuroprotection.

Topics: Animals; Benzimidazoles; Blood Pressure; Carotid Artery Diseases; Carotid Artery, Common; Drug Evaluation, Preclinical; Excitatory Amino Acids; gamma-Aminobutyric Acid; Glycine; Ischemic Attack, Transient; Male; Morpholines; Neostriatum; Neuroprotective Agents; Neurotransmitter Agents; Rats; Taurine

Influence of afobazole on cerebral blood flow in rats under conditions of global transient ischemia of brain, experimental myocardial infarction, and combined disturbances of coronary and cerebral circulation was studied in comparison to intact and sham operated animals. It is established that afobazole (5 mg/kg) enhances blood flow in parietal region of cerebral cortex of rats after global transient ischemia of brain or experimental myocardial infarction more prominently than in intact and sham operated animals. Moreover, the cerebrovascular effect of afobazole substantially increases under conditions of combined vascular pathology of brain and heart and exceeds its action observed after the cerebral ischemia or myocardial infarction.

Topics: Animals; Anti-Anxiety Agents; Benzimidazoles; Cerebrovascular Circulation; Coronary Occlusion; Ischemic Attack, Transient; Male; Morpholines; Rats