ABSTRACT
Experiments have shown that adamantane derivate - 5-hydroxyadamantan-2-on (100 mg/kg, i.v.) enhances the local blood flow in the cerebral cortex of rats under global transient brain ischemia conditions, while not influencing the brain blood flow in intact rats. In the same dose, adamantane derivate significantly decreases mortality in rats under conditions of hypergravity ischemia. The cerebrovascular effect of adamantane derivate is abolished by bicuculline (GABA-A receptor blocker), which is evidence for a GABAergic component in the mechanism of the cerebrovascular action ofadamantane derivate.
Subject(s)
Adamantane/therapeutic use , Antiparkinson Agents/therapeutic use , Cerebral Cortex/drug effects , Cerebrovascular Circulation/drug effects , Ischemic Attack, Transient/drug therapy , Adamantane/administration & dosage , Adamantane/analogs & derivatives , Animals , Antiparkinson Agents/administration & dosage , Bicuculline/administration & dosage , Blood Pressure/drug effects , Cerebral Cortex/blood supply , Cerebral Cortex/physiopathology , GABA-A Receptor Antagonists/administration & dosage , Ischemic Attack, Transient/mortality , Ischemic Attack, Transient/physiopathology , Laser-Doppler Flowmetry , Male , Rats , Receptors, GABA-A/metabolism , Survival RateABSTRACT
Experiments on rats showed that 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate increases cerebral blood flow in the system of carotid arteries both in intact animals and under conditions of global transient ischemia. In combination with tropoxin, 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate enhances the blood flow in the inner carotid artery of intact rats and the local blood flow under conditions of global transient ischemia. A combination of 2-ethyl-6-methyl-3-hydroxypyridine hemisuccinate and tropoxin increases baseline cerebral blood flow and decreases the constrictor reaction of cerebral blood vessels to 5HT(2B/2C) receptor agonist meta-chlorophenylpiperazine.
Subject(s)
Aza Compounds/therapeutic use , Brain Ischemia/drug therapy , Brain/drug effects , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Carotid Artery, Internal/drug effects , Cerebrovascular Circulation/drug effects , Neuroprotective Agents/therapeutic use , Picolines/therapeutic use , Animals , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Aza Compounds/administration & dosage , Brain/blood supply , Brain/physiopathology , Brain Ischemia/pathology , Brain Ischemia/physiopathology , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Carotid Artery, Internal/physiopathology , Disease Models, Animal , Drug Combinations , Male , Neuroprotective Agents/administration & dosage , Picolines/administration & dosage , Piperazines/administration & dosage , Piperazines/adverse effects , Rats , Serotonin Antagonists/administration & dosage , Serotonin Antagonists/therapeutic use , Serotonin Receptor Agonists/administration & dosage , Serotonin Receptor Agonists/adverse effectsABSTRACT
Metabolism of afobazole in rats has been studied using mass-spectrometry and HPLC, which revealed 17 products of afobazole biotransformation along with the parent compound. The structures of six afobazole metabolites were established and confirmed by comparison of HPLC retention times with the synthetic reference compounds and HPLC/mass spectrometry. Other metabolites were characterized by the masses of molecular ions. A significant fraction of the drug dose is biotransformed with the formation of hydroxylated benzimidazole moiety and oxidated morpholine.
Subject(s)
Anti-Anxiety Agents/metabolism , Benzimidazoles/metabolism , Morpholines/metabolism , Animals , Anti-Anxiety Agents/blood , Anti-Anxiety Agents/urine , Benzimidazoles/blood , Benzimidazoles/urine , Biotransformation , Chromatography, High Pressure Liquid , Male , Mass Spectrometry , Morpholines/blood , Morpholines/urine , RatsABSTRACT
Himantane introduced via a gastric tube to pregnant rats in a dose of 10, 30, 50, and 100 mg/kg produced a dose-dependent embryotoxic and teratogenic action. An analysis of the experimental results and published data suggests that the embryotoxicity of himantane can be related to its general toxic action upon the organism of pregnant female rats.
Subject(s)
Abnormalities, Drug-Induced/etiology , Adamantane/analogs & derivatives , Adamantane/toxicity , Antiparkinson Agents/toxicity , Embryonic and Fetal Development/drug effects , Pregnancy Complications/chemically induced , Animals , Female , Lethal Dose 50 , Pregnancy , RatsABSTRACT
A total of 329 novel adamantane derivatives have been synthesized and pharmacologically studied. Among them, the compounds containing halogen-containing aromatic radicals in the second position show the most pronounced effect on animal resistance to the emergencies induced by its habitat and performance. N-(2-adamantyl)-N-(para-bromphenyl)amine (bromantane) possesses a low toxicity, a high ability to enhance the physical and operant working maintenance of animals, to accelerate its recovery in developed fatigue, in hyperthermia and hypoxia in particular. 2-(para-chlorobenzoylamine)adamantane (chlodantane) has the processes of a rapid-action adaptogenic agent by enhancing the resistance of animals to various physical and toxically chemical noxious agents. The two compounds have immunostimulating effects in secondary stress-induced immunodeficiencies whose mechanism of action is a membranous protective activity.
Subject(s)
Adamantane/analogs & derivatives , Amantadine/analogs & derivatives , General Adaptation Syndrome/prevention & control , Psychotropic Drugs/pharmacology , Amantadine/pharmacology , Animals , Humans , Mice , Rats , Stress, Psychological/drug therapyABSTRACT
The experiments on rats showed that of 16 studied imidazo [1,2-a]benzimidazole derivatives only the compounds with phenyl at the second carbon atom and nitrogen-containing radical of the ninth nitrogen atom inhibit the gastric acid secretion. The binding of oxymethyl group to phenyl, its substitution through adamantyl, displacement of nitrogen-containing substitute to the first nitrogen atom or its substitution were found to decrease or stop the inhibiting action of these substances on the gastric parietal cells. Dihydrochloride 2-phenyl-9 (beta-diethyl-aminoethyl)imidazo [1,2-a]denzimidazole was more potent than cimetidine and omeprazole in inhibiting the gastric acid secretion, pepsin output and antiulcer action.