Neuroprotective effects of lamotrigine enhanced by flunarizine in gerbil global ischemia.
We examined whether the anti-ischemic effect of lamotrigine (LTG), which inhibits the presynapic sodium channel, could be enhanced by the calcium channel blocker-flunarizine (FNR) in cerebral ischemia. Global ischemia was induced in Mongolian gerbils for 5 min under the monitoring of scalp temperature. LTG and FNR were administered intraperitoneally 1 h before ischemia. After 7 days, animals were killed and viable neurons in CA1 area were counted. LTG treated group showed significant protective effects compared to control group (P < 0.01). These effects were more prominent in group treated with LTG and FNR (P = 0.01). Combination of two drugs did not increase the mortality rate compared to single-treated group. These results show that a synergistic reduction of neuronal death can be achieved by combination of LTG and FNR without serious adverse reaction.
D000818:Animals; D001921:Brain / Q000098:blood supply; D001923:Brain Chemistry / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002544:Cerebral Infarction / Q000188:drug therapy; D004357:Drug Synergism; D005444:Flunarizine / Q000494:pharmacology*; D005849:Gerbillinae; D000077213:Lamotrigine; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology; D014227:Triazines / Q000494:pharmacology*