Abstract
Benzodiazepine derivatives are among the most popular anxiolytic drugs. The most serious negative drawbacks of this group of drugs are their amnesiogenic nature, increased tolerance of psychotropic effects, and dependence. This paper analyzes the CNS mechanisms responsible for tolerance and dependence. On the basis of a review of biochemical, electrophysiological and behavioural animal studies the author suggests that both these phenomena may be caused by gradual development of hypoactivity of the central GABA-ergic system which is related to GABA-A receptors. At the cellular level this process is manifest in the weakening of the intensity of the chloride current triggered by the GABA-A receptor which leads to weaker inhibition of the limbic structures responsible for emotional mediation. In light of this conception of benzodiazepine tolerance development the group of partial antagonists of the benzodiazepine receptor (bretazenil, imidazenil) and selective agonists of the benzodiazepine 1, i.e., omega-1, receptor (alpidem, zolpidem) present themselves favourably. Because they have a weaker stimulating effect on the GABA-A receptor or affect only a fraction of this receptor type, these groups of medications do not cause excessive readjustment of the GABA-energic system and leave room for the activity of the endogenic neurotransmitter – gamma aminobutyric acid. This leads to weaker tolerance development.