involvement of GABA-ergic transmission in the anticonvulsant effect of ginkgo biloba against kainic acid-induced seizures in mice

Ginkgo biloba[GbE] is an herbal product that has been proven to be effective in many neurological disorders. However, its anticonvulsant activity is not sufficiently studied. The aim of this work is to study the anticonvulsant activity of GbE and the role of GABA-ergic transmission in this effect.[1] Studying the anticonvulsant activity of GbE in different dose levels [20, 30 and 50 mg/kg/d, orally] for 15 days against kainic acid [KA]-induced seizures in mice. [2] Measurement of the brain giutamate and GAB A levels and glutamate decarboxylase [GAD] activity. GbE showed a protective effect for animals against KA-induced seizures in a dose-related manner. This appeared in form of a significant increase in time of seizure onset and decrease in percent of seizures and mortality in animals treated with GbE. Furthermore, there was a significant decrease in brain glutamate level and increase in GABA level and GAD activity in GbE-treated groups relative to KA-treated group. From the obtained results, we can conclude that GbE has effective anticonvulsant activity against KA-induced seizures. This effect may be mediated via various mechanisms but GABA-ergic transmission plays a vital role in this effect. Future research directions include further studies of the other possible mechanisms of GbE involved in its anticonvulsant and neuropotective activity

Synthesis and docking study of some pyrazolo [3, 4-d] pyrimidin -4 [5H]-one derivatives as phosphodiesterase-5 inhibitors

Twelve new pyrazolo [3, 4-d] pyriniidin-4-[5H]-one derivatives 13a-g, 14-17 and 24 were synthesized as inhibitors of phosphodiesterase enzyme type 5 [PDE5]. All intermediates and final compounds were analyzed by IR, H-NMR, mass spectra and elemental analysis. The title compounds were evaluated for their inhibitory activity toward PDE5 in comparison with sildenafil using anaesthetized normotensive rabbits. Eleven of the final compounds 13 a-g, 14, 16 and 24 were subjected to biological screening using animal model and nine of these compounds were subjected to molecular modeling study in order to investigate their binding mode. Most of the explored tested compounds showed the same binding mechanism as vardenafil and some of these compounds showed promising activity in comparison to sildenafil in the pharmacological studies. The results indicated that compound 24 is the most active member of the investigated series