Experimental Substantiation of the Use of Phenibut Combinations with Salicylic, Nicotinic, and Glutamic Acids in Cerebral Ischemia.

Abstract

One of the possible ways to increase the effectiveness of drugs based on gamma-aminobutyric acid derivatives is to introduce biologically active acids into their structure. In this regard, the compositions of phenibut with organic acids, which have a more pronounced psychotropic activity, low toxicity, and good tolerability, are of interest. The purpose of this study is to experimentally substantiate the use of phenibut combinations with organic acids in various forms of cerebral ischemia. The study was performed on 1210 male Wistar rats weighing 180-220g each. The cerebroprotective activities of phenibut combinations with salicylic acid (2:1, doses of 15, 30, and 45mg/kg), nicotinic acid (2:1, doses of 25, 50, and 75mg/kg), and glutamic acid (2:1, doses of 25, 50, and 75mg/kg) have been studied. The study involved a single prophylactic administration of phenibut combinations with organic acids and a 7days course of the combination treatment administered at doses that proved the most effective according to the results of a single prophylactic administration. The rate of local cerebral blood flow and the vasodilating function of cerebral endothelium were measured, and the researchers evaluated the effects of the studied phenibut combinations on biochemical parameters in rats with focal ischemia. Compositions of phenibut with salicylic, nicotinic, and glutamic acids in subtotal and transient cerebral ischemia were found to have the most pronounced cerebroprotective effect in doses of 30, 50 and 50mg/kg, respectively. Under reversible 10min occlusion of the common carotid arteries, prophylactic administration of the studied phenibut compositions prevented a decrease in cerebral blood flow during ischemia and reduced the severity of postischemic hypoperfusion and hyperperfusion. At a course of 7days of therapeutic administration of compounds, their pronounced cerebroprotective effect was observed. The data obtained can be considered as promising the pharmacological search in this series of substances for the treatment of patients with cerebrovascular disease.