Abstract:
Effects of a propyloxy derivative of 1.4-benzodiazepine, propoxazepam, on GABA-benzodiazepine
receptor complexes (GABA RCs) were examined in vitro and in vivo. The parameters of propoxazepam
binding to synaptosomes from the rat brain were estimated in vitro. The Ki constant for inhibition
of [3H] flumazenil binding by this agent was 3.5 ± 0.3 nM, on average. Considering the value of
the GABA shift (1.9), propoxazepam can be considered as GABA-RC full agonist. On the model of
picrotoxin-induced seizures in vivo, the propoxazepam average effective dose was estimated as 4.1 ±
± 0.21 mmol/kg. It was found that the parameters of myoclonic components (latent period of the onset of
myoclonic seizures and their number), as well as death time of the tested animals, characterize adequately
an anticonvulsant action of propoxazepam of picrotoxin-induced seizures in mice. Competitive
interaction with picrotoxin is the possible mechanism of these effects at the level of GABAARCs.
Significant deviations from a competitive model of monomolecular and cooperative binding of the agent
at the receptor level have been found.
