ABSTRACT

Rationale: The positive allosteric modulation of the GABAA receptor complex by neurosteroids may be an important new approach for antiepileptic interventions. Ganaxolone (GNX) is the first synthetic analogue of Allopregnanolone, an endogenous neurosteroid. Objective: To evaluate and compare the antiepileptic effect of GNX with sodium valproate (SV) and the combined antiepileptic effect of GNX in combination with SV on two seizure models in male albino wistar rats Methods: A total of 60 rats were divided into 5 groups, each containing 6 rats for each seizure model. Group 1 was treated with 40% Hydroxypropyl-?-Cyclodextrin i.p, group 2,3 received GNX 5mg/kg and 10mg/kg i.p respectively, group 4 received SV 200 mg/kg i.p. and group 5 was given GNX 5 mg/kg and SV 100 mg/kg i.p. The ability to abolish the Tonic Hind Limb Extension component was selected as the anticonvulsant activity criteria in the Maximal Electroshock (MES) induced model. The latency period and duration of seizures were studied in the pentylenetetrazol (PTZ) induced model. Results: Our study revealed that GNX (10 mg/kg) and combination of GNX 5 mg/kg with SV 100 mg/kg has promising antiepileptic effect in both the models. The combination of SV and GNX is additive, but not synergistic or supra-additive. Conclusions: The results of our study calls for future experiments to assess the therapeutic effect of GNX and its combination with available antiepileptic drugs and compare it for mono or polytherapy, based on the balance of adverse effects and efficacy. Keywords: Ganaxolone, Neurosteroids, Sodium valproate, PTZ, MES
Publication date: 01/07/2020

https://ijbpas.com/pdf/2020/July/MS_IJBPAS_2020_5098.pdf

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https://doi.org/10.31032/IJBPAS/2020/9.7.5098