Evidence for the involvement of the GABA- ergic pathway in the anticonvulsant and antinociception activity of Propoxazepam in mice and rats
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Bogatsky Physical-chemical instityte of NAS, Odessa, Ukraine
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Vitalii Larionov   

Bogatsky Physical-chemical instityte of NAS of Ukraine, Lyustdorfskaya doroga 86, 65080, Odessa, Ukraine
J Pre Clin Clin Res. 2019;13(3):99-105
Propoxazepam (3-alcoxyderivative of 1.4-benzodiazepine), in the tail-flick test and picrotoxin-induced convulsions showed significant analgesic and antiepileptic activity. Flumazenil (GABA antagonist) reduced its analgesic action, although antiseizure activity was changed slightly. As specific propoxazepam actions are anticonvulsant (1 subtype GABAA-R) and analgesic (2 subtype GABAA-R in the spinal cord), it can be suggested that the substance has no abuse-related side-effects.

Material and methods:
The possible involvement of the GABA system in the antinociceptive effect of propoxazepam was examined by administering flumazenil (1 and 10 mg/kg, i.p.), a selective GABA- receptor antagonist, 30 min prior to propoxazepam (1.8 and 10 mg/kg, orally) in rats. Picrotoxin solution (6.5 mg/kg, 95 % of lethality effect in mice) was injected subcutaneously 30 min after propoxazepam administration. Flumazenil was administered intraperitoneally 0.5 hour prior to propoxazepam administration. Time counting was starting from the convulsant injection and during the supervision time, the number of myoclonic convulsions and tonic extensia, time of their onset, as well as time to lethal effect (survival time), were registered.

Flumazenil and propoxazepam antiseizure effect in the picrotoxin-induced seizures test were estimated as 5.24±2.38 and 0.37±0.07 mg/kg. Antiseizure effect of propoxazepam was reduced with flumazenil administration. Flumazenil (1 mg/kg) had no effect in tail-flick test but abolished the antinociceptive action of propoxazepam (tail flick latency period changes were -1.6% and +55.1, compared to control and propoxazepam alone administration, respectively).

The mechanism of propoxazepam antiseizure and antinociceptive actions are GABA-R determined. Analgesic action mechanism assumes additional biotargets involvement.

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