RESUMO
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.
Assuntos
Adamantano/uso terapêutico , Antiparkinsonianos/uso terapêutico , Córtex Cerebral/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Ataque Isquêmico Transitório/tratamento farmacológico , Adamantano/administração & dosagem , Adamantano/análogos & derivados , Animais , Antiparkinsonianos/administração & dosagem , Bicuculina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiopatologia , Antagonistas de Receptores de GABA-A/administração & dosagem , Ataque Isquêmico Transitório/mortalidade , Ataque Isquêmico Transitório/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Ratos , Receptores de GABA-A/metabolismo , Taxa de SobrevidaRESUMO
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.
Assuntos
Compostos Aza/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Artéria Carótida Interna/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Picolinas/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Compostos Aza/administração & dosagem , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Artéria Carótida Interna/fisiopatologia , Modelos Animais de Doenças , Combinação de Medicamentos , Masculino , Fármacos Neuroprotetores/administração & dosagem , Picolinas/administração & dosagem , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Ratos , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/uso terapêutico , Agonistas do Receptor de Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/efeitos adversosRESUMO
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.
Assuntos
Ansiolíticos/metabolismo , Benzimidazóis/metabolismo , Morfolinas/metabolismo , Animais , Ansiolíticos/sangue , Ansiolíticos/urina , Benzimidazóis/sangue , Benzimidazóis/urina , Biotransformação , Cromatografia Líquida de Alta Pressão , Masculino , Espectrometria de Massas , Morfolinas/sangue , Morfolinas/urina , RatosRESUMO
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.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Adamantano/análogos & derivados , Adamantano/toxicidade , Antiparkinsonianos/toxicidade , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Complicações na Gravidez/induzido quimicamente , Animais , Feminino , Dose Letal Mediana , Gravidez , RatosRESUMO
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.
Assuntos
Adamantano/análogos & derivados , Amantadina/análogos & derivados , Síndrome de Adaptação Geral/prevenção & controle , Psicotrópicos/farmacologia , Amantadina/farmacologia , Animais , Humanos , Camundongos , Ratos , Estresse Psicológico/tratamento farmacológicoRESUMO
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.