COMPARATIVE ANALYSIS OF THE RU-476 COMPOUND INFLUENCE AND IDENTIFIED 5-HT2A ANTAGONISTS ON THE BLOOD FLOW VELOCITY IN THE MEDIAL CEREBRAL ARTERY

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In practical medicine the whole range of drugs which correct transitory cerebrovascular disorders and hemostasis disturbance including migraine, which were proved to have 5-HT2A-antagonist activity. Previously the capability of new blocker of 2A serotonin receptor RU-476 were shown, as well as the capability of identified 5HT2A-antagonists to reduce a cramp in carotid vessels provoked by serotonin. In this connection, it is timely to study the influence of RU-476 compound on the velocity of blood flow in the vessels of temporoparietal area of brain in conditions of serotonin stress. Purpose of the work was to carry out an analysis of the influence of new 5HT2A-antagonist RU-476 on the expansion of serotonin-induced reduction of the blood flow velocity in medial cerebral artery. Materials and methods of the study: we carried out the investigation using outbred male rats. We registered the dynamics of a blood flow by using Doppler sonography with serotonin stress in the projection of the medial cerebral artery, by using a previously described method. To study the level of 5-HT2A-blocking action of the new compound we examined the effects of more active and identified 5-HT2A-antagonists of ritanserin, ketanserin, cyproheptadine, and methysergide. The substances under study were injected intravenously in the equimolar doses. The data obtained were compared with the control group rates. Results: in the control group, serotonin reduced the brain blood flow by 40.3±4.39% with the injection at dose 20 µg/kg during the first minute. As the result of the tests of the identified antagonist we have established that 5-HT2A-blockers relevantly reduced serotonin-induced the fall of the velocity of a blood flow in the area of the medium cerebral artery more than by 50%. Among them, methysergide exhibited the highest activity, which reduced the effects of 5-hydroxitriptamine in 2.8 times. A new blocker of 2A serotonin receptors RU-476 was more effective to some extent, reduced the fall of the blood flow velocity provoked by the serotonin approximately 5 times and exceeded the effects of the 5-HT2-antagonists (ritanserin and cyproheptadine). Conclusions: thus, we have established that RU-476 compound not even was capable to effectively block the reduction of a blood flow velocity in the area of medium cerebral artery provoked by the serotonin, exceeding the comparison drugs (ritanserin and cyproheptadine).