Dichloro-substituted phenyl amino propanamides exhibit anticonvulsant effect and reduce inward sodium ion current (NaV1.6)

Publication date: Available online 28 June 2017 Source:Egyptian Journal of Basic and Applied Sciences Author(s): S. Malami, A.Y. Idris, A.H. Yaro, J.A. Anuka, I.M. Hussaini, M.K. Patel This research studied the anticonvulsant properties of three synthesized isomers of dichloro-substituted phenyl amino propanamides in rodents and determined their effects on votage-gated sodium channels (NaV1.6) stably expressed in Human Embryonic Kidney (HEK Cells 293). 2,3-, 2,5- and 3,4- Dichloro anilines were reacted with acrylamide according to Michael-type addition reaction to obtain their corresponding isomers; DCP23, DCP25 and DCP34. Each isomer was evaluated for anticonvulsant effects using maximal electroshock (MES)- and pentylenetetrazole (PTZ)- induced seizure models in mice; tested against PTZ-induced kindling in rats and its synergistic effect with fluphenamic acid in mice. Effects of the compounds were studied on voltage-gated sodium channels (NaV1.6) at different states of the channel, using electrophysiology techniques. The test compounds generally offered dose dependent protection against maximal electroshock- and pentylenetetrazole (PTZ)- induced seizure; demonstrated synergistic effect when co-administered with fluphenamic acid; and produced significant (p <0.05) decrease in seizure progression in PTZ-kindled rats. DCP23 and DCP25 reduced sodium currents at different channel states in a concentration dependant manner. The results of this study showed that the ...
Source: Egyptian Journal of Basic and Applied Sciences - Category: Science Source Type: research