Khodakovsky O. Pathogenetic background of new adamantane derivatives use reasonability in brain and myocardial acute ischemia experimental therapy (experimental investigation)

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0515U000008

Applicant for

Specialization

  • 14.03.05 - Фармакологія

23-12-2014

Specialized Academic Board

Д 41.600.01

Odessa National Medical University

Essay

This thesis deals with increase for pharmacotherapy of cerebral perfusion disorders and myocardial infarction, by application of NMDA-receptors’ modulator 1-adamantiloxy-3-morpholino-2-propanolhydrochloride (ademol), which, due to corrective effect on development of glutamate neurotoxicity and influence on the key intracellular factors of pathobiochemical cascade in neurons and cardiomyocytes (including apoptotic programs), promotes the realization of principles for primary cerebro- and cardioprotection. During the investigation of models acute cerebral and myocardial ischemia, was determined, that ademol expressed the maximal cerebroprotective and cardioprotective activity with apparent dose-dependence. Ademol protective effect was not only comparable but sometimes exceeded the effect of cyticolinum, piracetam, mexidolum, actovegin, thiotriazoline, corvitin, which was indicated by its ability to reduce lethality, postpone the death of test animals, improve their neurologic status and mnestic functions in conditionally effective doses. The complex mechanism of ademol cerebroprotective and cardioprotective action in case of acute cerebral perfusion disorder and myocardial infarction is associated with modulating influence on NMDA-receptors’ activity, stimulation of cerebral and cardiac perfusion; elimination of energy deficiency, metabolic acidosis, neuron and cardiomyocyte oxidant injury; corrective effect on nitrogen monoxide metabolism, preservation of architectonic of both organs due to mechanisms including reduction of apoptosis.

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