Carbetapentane attenuates kainate-induced seizures via sigma-1 receptor modulation.
We examined the effects of a non-opioid antitussive, carbetapentane (CB) on kainic acid (KA)-induced neurotoxicity in rats. KA administration (10 mg/kg, i.p.) produced robust behavioral convulsions lasting 4 to 5 h. CB (12.5 and 25 mg/kg. i.p.) pretreatment consistently and in a dose-dependent manner reduced the KA-induced seizures, mortality, and marked loss of cells in regions CA1 and CA3 of the hippocampus. Consistently, CB pretreatment also significantly attenuated the KA-induced increase in Fos-related antigen immunoreactivity in the hippocampus. In contrast, pretreatment with the sigma-1 receptor antagonist BD1047 (1 and 2 mg/kg, i.p.) blocked, in a dose-related manner, the neuroprotection afforded by CB. These results suggest that CB provides neuroprotection against KA insult via sigma-1 receptor modulation.
Kim
H C
HC
Department of Pharmacy, College of Pharmacy, Korea Institute of Drug Abuse, Kangwon National University, Chunchon. kimhc@cc.kangwon.ac.kr
Jhoo
W K
WK
Kim
W K
WK
Shin
E J
EJ
Cheon
M A
MA
Shin
C Y
CY
Ko
K H
KH
D000818:Animals; D048588:Benzoxazines; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology*; D004347:Drug Interactions; D007150:Immunohistochemistry; D007608:Kainic Acid; D008297:Male; D010078:Oxazines; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced*; D000097605:Sigma-1 Receptor
D048588:Benzoxazines; D003517:Cyclopentanes; D007608:Kainic Acid; D010078:Oxazines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C028911:cresyl violet; C018861:carbetapentane