ABSTRACT
The influence of afobazole on the accumulation of free radical oxidation products (reactive oxygen species, ROS) and on the activity of antioxidative enzyme catalase was studied in striatum and cortex of rats under cerebral ischemia damage conditions. Afobazole showed a tendency to decrease the extent of ROS accumulation in the cortex. In striatum, the intensity of ROS accumulation in rats after ischemia wasa reliably lower as compared to that in control rats, but afobazole produced a partial recovery of this parameter. Afobazole induced an increase in the catalase activity in the cortex of rats with ischemia. In contrast, afobazole did not change the activity of this enzyme in striatum (where it was also decreased by ischemia). Thus, afobazole increased the resistance of neuron membrane structures to free radical oxidation in cortex and striatum and stimulated the catalase activity in the cortex in rats with global reversible cerebral ischernia.
Subject(s)
Benzimidazoles/therapeutic use , Brain Ischemia/drug therapy , Catalase/metabolism , Morpholines/therapeutic use , Neuroprotective Agents/therapeutic use , Reactive Oxygen Species/metabolism , Animals , Benzimidazoles/pharmacology , Brain Ischemia/enzymology , Brain Ischemia/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/enzymology , Cerebral Cortex/metabolism , Corpus Striatum/drug effects , Corpus Striatum/enzymology , Corpus Striatum/metabolism , Enzyme Activation , Morpholines/pharmacology , Neostriatum/drug effects , Neostriatum/enzymology , Neostriatum/metabolism , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/pharmacology , Oxidation-Reduction , RatsABSTRACT
The role of GABAergic mechanisms in realization of the effects of afobazole and picamilon on the cerebral circulation was studied in rats. It is found that the cerebrovascular effect of afobazole significantly decreases on the background of the GABA receptor antagonists bicuculline and picrotoxin. This is evidence of an important role of the GABA system in the its cerebrovascular and neuroprotective activity of afobazole. The results of experiments with picamilon showed that the cerebrovascular effect of this drug is not affected by receptor blocking with bicucullin. However, the blocking of chloride channels of the GABA receptors by picrotoxin significantly decreased the effect of picamilon on the cerebral blood flow.
Subject(s)
Analgesics/administration & dosage , Benzimidazoles/administration & dosage , Cerebellum/blood supply , Morpholines/administration & dosage , Receptors, GABA/metabolism , gamma-Aminobutyric Acid/analogs & derivatives , gamma-Aminobutyric Acid/administration & dosage , Animals , Bicuculline/administration & dosage , Cerebellum/metabolism , GABA Antagonists/administration & dosage , Picrotoxin , Rats , Regional Blood Flow/drug effectsABSTRACT
The selective anxiolytic drug afobazole administered in a dose of 5 mg/kg increased the cerebral blood flow in rats. The effect was more pronounced in rats with global reversible cerebral ischemia than in intact animals. The ischemia model was caused by occlusion of both common carotid arteries for 120 min with simultaneous reduction of the arterial pressure to 40-50 mm Hg through blood-letting. Afobazole also significantly increased the survival of rats with cerebral ischemia model caused by ligation of both common carotid arteries, which was evidence of the neuroprotector activity. Apparently, the ability of afobazole to improve the cerebral blood flow in ischemized rat brain is an important factor in realization of the neuroprotector activity.
