Opposite effects of ethanol and nitrendipine on nicotine-induced emesis and convulsions.
The effects of ICV injections were investigated in unanesthetized cats of ethanol alone and in combination with the dihydropyridine calcium antagonist, nitrendipine, on emesis and the convulsions produced by nicotine, which was similarly injected by the ICV route. In the first series of experiments, short lasting convulsions and emesis were the most prominent symptoms after the ICV injection of nicotine in a dose of 1.0 mg. In the second series of experiments the pretreatment of cats with ethanol given ICV in doses of 0.03, 0.2, and 0.3 ml reduced the emesis and prevented the convulsions induced by 1.0 mg dose of ICV nicotine. In the third series of experiments, the ICV injection of nitrendipine in doses of 0.024, 0.16, and 0.24 mg incorporated in the solution of ethanol, given in volumes of 0.03, 0.2, and 0.3 mt, respectively, blocked emesis but not the convulsions induced by the 1.0 mg dose of nicotine given ICV. The results suggest, therefore, that at least two different mechanisms underlie these phenomena. First, the synergistic effects at the neuronal nicotinic ionophores in the brain would act to underlie the antagonistic action of ethanol and nitrendipine on the emetic response. Second, conformational changes brought about by ethanol at voltage-dependent calcium channels in the brain may antagonize the inhibitory effect of the dihydropyridine calcium antagonist, producing the reversal of convulsions.
Samardzic
R
R
Department of Pharmacology, Faculty of Medicine, Belgrade, Yugoslavia.
Bajcetic
M
M
Beleslin
D B
DB
D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D002415:Cats; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D000431:Ethanol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D008297:Male; D009538:Nicotine; D018722:Nicotinic Agonists; D009568:Nitrendipine / Q000008:administration & dosage / Q000627:therapeutic use*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D002121:Calcium Channel Blockers; D002492:Central Nervous System Depressants; D004338:Drug Combinations; D018722:Nicotinic Agonists; D000431:Ethanol; D009538:Nicotine; D009568:Nitrendipine