АНТИКОНВУЛЬСАНТИ, ЩО МАЮТЬ ГАМК-ЕРГІЧНИЙ МЕХАНІЗМ ДІЇ

Анотація

ANTICONVULSANTS WITH GABAERGIC MECHANISM OF ACTION

L.O. Perekhoda

NationalUniversityofPharmacy, Kharkiv

Summary: A literary review of modern anticonvulsants that have predominantly GABAergic mechanism of action was given. Perspective directions of chemical modification will choose and recommendations for the search of the most promising ways of modification which allow to improve the efficiency of the search of new anticonvulsants that have predominantly GABAergic mechanism of action were summarized.

Keywords: epilepsy, mechanism of action, GABA, anticonvulsant.

Introduction. The treatment of epilepsy is important because of the high prevalence of the disease and complex social, legal and economic issues associated with it. During the last decades there were new anticonvulsants, but unfortunately they have many side effects, so we need to continually improve drug therapy by expanding arsenal of anticonvulsants. In turn, the detailed study of the mechanism of action and the establishment of relations "structure - anticonvulsant activity" in the ranks of existing drugs require to expand arsenal of anticonvulsants. Analysis of the mechanism of action of anticonvulsants proves the existence of three mechanism (GABAergic, glutamatergic, direct influence on the regulation of electric pulse ion channels of neurons) predominant of which is GABAergic. The recognition of the role of GABAergic system violation in the development of seizures became the stimulus for the development of anticonvulsants affecting different parts of the GABAergic synaptic transmission.

Methods. To achieve the goals and objectives the methods of information retrieval and comparative analysis were used.

Results and discussion. Analyzing the published data we found that anticonvulsants affecting different parts of the GABAergic synaptic transmission are quite promising matrix based on which the search of new anticonvulsants can be done. One of the directions of the search of anticonvulsants activating GABAergic transmission was realized by the creation of drugs which are structurally similar to GABA. In this paper the examples of structures of the drugs which are structurally similar to GABA (Phenigaba, Lyoresalum, Gamibetalum) and possess an anticonvulsant effect were shown, the influence of substitution or the hirality on  the activity of the molecular was explained. The second directions of the search of anticonvulsants activating GABAergic transmission was realized by the creation of the drugs, which are GABA agonists (benzodiazepines, barbiturates and derivatives of hydantoin). The paper has shown two groups of GABA agonists (benzodiazepines and barbiturates), which were compared with each other from the viewpoint of the effectiveness and safety. The detailed study of the prospective structures in the series of the agonists GABA receptor and the summarizing of the progress of recent years will allow to choose the most promising ways of modification in order to improve the search of the efficiency of new anticonvulsants. The relationship "structure-activity" among the group of barbiturates and general ways of metabolism of drugs in this group (Benzobarbitalum, Benzobamilum, Hexamidinum) have been analyzed.

Conclusions. The relationship "structure-activity" among modern anticonvulsants with predominantly GABAergic mechanism of action has been analyzed. Perspective directions of chemical modification and recommendations for further search of anticonvulsants with GABAergic action have been generalized.