m-Trifluoromethyl-diphenyl diselenide attenuates pentylenetetrazole-induced seizures in mice by inhibiting GABA uptake in cerebral cortex slices.
The present study investigated the anticonvulsive effect of the disubstituted diaryl diselenides diphenyl diselenide (PhSe)(2), m-trifluoromethyl-diphenyl diselenide (m-CF(3)-C(6)H(4)Se)(2), p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) and p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) on a chemical model of seizure induced by pentylenetetrazole (PTZ) in mice. (PhSe)(2), (p-Cl-C(6)H(4)Se)(2) and (p-CH(3)O-C(6)H(4)Se)(2) did not abolish seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) at the dose of 100 mg/kg significantly prolonged the latency of the onset of the first convulsive episode and reduced the number of animals that presented seizures. To investigate the possible mechanisms involved in the anticonvulsant effect of (m-CF(3)-C(6)H(4)Se)(2), mice were submitted to different associations (all drugs in a sub-effective dose); aminooxyacetic acid hemihydrochloride (AOAA, a gamma-aminobutyric acid (GABA)-T inhibitor), diazepam (a GABA(A) receptor agonist) or DL-2,4-diamino-n-butyric acid hydrochloride (DABA, an inhibitor of GABA uptake) were pre-administered together with (m-CF(3)-C(6)H(4)Se)(2). (m-CF(3)-C(6)H(4)Se)(2) + DABA abolished seizures induced by PTZ in mice. (m-CF(3)-C(6)H(4)Se)(2) administered alone or with PTZ decreased the levels of GABA uptake in cerebral cortex slices. The present study demonstrates that (m-CF(3)-C(6)H(4)Se)(2) exerts anticonvulsant action by decreasing the levels of GABA uptake.
Prigol
Marina
M
Department of Chemistry, Natural Science Institute, Federal University of Santa Maria, Santa Maria, 97105-900, RS, Brazil.
Brüning
César A
CA
Godoi
Benhur
B
Nogueira
Cristina W
CW
Zeni
Gilson
G
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology; D017646:Organosilicon Compounds / Q000494:pharmacology*; D010433:Pentylenetetrazole; D012640:Seizures / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D017646:Organosilicon Compounds; C546861:m-trifluoromethyl-diphenyl diselenide; C061132:diphenyldiselenide; D005680:gamma-Aminobutyric Acid; D010433:Pentylenetetrazole