Abstract
Some of highly effective antiepileptic substances share the polymodal pharmacological action which determines the possibility of their use for treatment of pathogenetically similar diseases. Inhibitory mediator systems influence for example, suggests the combination in the pharmacological spectrum such actions as antiepileptic, analgesic (antineuropathic) and other actions.
 The aim of the study was evaluation of anticonvulsant effect of 7-bromo-5-(o-chlorophenyl)-3-propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) on the model of 4-aminopyridine (4-AP) – induced myoclonic seizures and characterization of its possible participation in modulation of the function of voltage-dependent potassium channels.
 4-AP (10.3 mg/kg, subcutaneously) was administered 30 minutes after intraperitoneal administration of propoxazepam different doses (20, 28, 40, 60 and 80 mg/kg) and the time and quantity of myoclonic and tonic convulsions as well as total time to the lethal effect were evaluated.
 It was found that in this model, propoxazepam possess moderate activity (ED50 = 37,3 ± 7.9 mg/kg) Even at high doses (80 mg/kg) of the test compound, anticonvulsive action did not reach 100%. The quantity of myoclonic seizures and the latency time of their onset have no statistically significant differences in comparison with the data of animals of the control group. On the contrary, the number (and percentage representation) of tonic convulsions in the common seizure episode increased, which is due to the possible inhibitory effect of propoxazepam, which is carried out primarily through GABA-ergic mechanisms.
Highlights
The epilepsies constitute a family of disorders characterized by spontaneous disturbances in the normal electrical activity of the brain associated with changes in behavior
Most clinically significant antiepileptic drugs (AEDs) have their principal actions on four classes of ion channels, the central currency of membrane excitability: these include chloride channels associated with inhibitory GABA, receptors, ligand-gated sodium and calcium channels associated with inotropic excitatory glutamate receptors (NMDA, N-methyl-Daspartate; AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid), kainate; voltage-dependent sodium channels and voltage-dependent calcium channels)
A radio-ligand binding assay [7] on rat membranes to determine the target receptor of propoxazepam showed that substance had a strong affinity for the central benzodiazepine binding site of GABAA – receptor (GABA-R)
Summary
The epilepsies constitute a family of disorders characterized by spontaneous disturbances in the normal electrical activity of the brain associated with changes in behavior (seizures). Both the electrical and the behavioral aspect of seizures can be quite variable and complex, even in a single patient. Propoxazepam had shown high activity on the model of GABA-deficient thiosemicarbazide-induced convulsions [6]. A radio-ligand binding assay [7] on rat membranes to determine the target receptor of propoxazepam showed that substance had a strong affinity for the central benzodiazepine binding site of GABAA – receptor (GABA-R). Calculations have shown that GABA-shift for propoxazepam is 1.9, which allows it to regard it as full GABA-R agonist
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
