Possible Interaction: Ethanol and Nitrendipine

“Dihydropyridine calcium channel antagonists, such as nitrendipine , have been previously found to prevent some of the adaptive responses to chronic ethanol intake.”

“However, the potentiation after in vivo administration of ethanol plus nitrendipine was significantly greater than after ethanol alone.”

“When LTP was produced by a transient increase in the calcium concentration in the bathing medium, the chronic ethanol treatment did not alter the potentiation of the population spike height, but in vivo treatment with ethanol plus nitrendipine decreased the potentiation.”

“Repeated administration of nitrendipine blocked the antinociceptive effects of chronic ethanol and prevented the hyperalgesia produced by ethanol withdrawal.”

“The highest dose of nitrendipine (10 mg/kg, twice daily) reduced consumption of the ethanol diet.”

“In the third series … ICV injection of nitrendipine in doses of 0.024, 0.16, … mg incorporated in the solution of ethanol , given in volumes of 0.03, 0.2, and 0.3 mt, respectively, blocked … the convulsions induced by the 1.0 mg dose of nicotine given ICV.”

“In the locomotor studies, both felodipine and nitrendipine significantly decreased the locomotor stimulation produced by ethanol ; the effects of the two compounds were similar, but dose-dependency was not seen at the doses tested.”

“The increases in handling-induced behavior … in mice during withdrawal from chronic ethanol treatment were prevented … administration of nitrendipine , 50 mg/kg, but not by, felodipine, 10 mg/kg, a dose that caused a similar displacement of dihydropyridine binding in central nervous system tissue, in vivo and in vitro.”

“Withdrawal from the ethanol chronic treatment increased the thresholds to seizures produced by intravenous aminophylline; this change was also prevented by nitrendipine.”

“It is known that co-administration of dihydropyridine derivative nitrendipine suppresses the development of physical dependence on ethanol.”

“The density of cerebral cortical A1-adenosine receptors and of nitrendipine binding sites on calcium channels were significantly increased after chronic ethanol , while the density of striatal A2a-adenosine receptors were unchanged.”

“4 Nitrendipine (50 mg kg−1) prevented the behavioural signs of ethanol withdrawal as measured by handling induced convulsions, but felodipine (10 mg kg−1 or 2 mg kg−1) did not provide any protection against this effect of ethanol withdrawal.”

“Suggested explanations for the results include the possibility that nitrendipine may protect against the ethanol withdrawal syndrome via sites other than dihydropyridine receptors: that felodipine has partial agonist actions at dihydropyridine receptors in the CNS or that felodipine has actions which mask its protective effect in ethanol withdrawal.”

“ Nitrendipine (25-100 mg/kg) was unable to reverse the anxiogenic responses detected on withdrawal from ethanol , but the highest dose did reduce withdrawal tremor.”

“1 Chronic treatment with the dihydropyridine calcium channel antagonist, nitrendipine , given concurrently with ethanol , prevented the ethanol withdrawal syndrome in mice, even though the chronic nitrendipine treatment was stopped 24 h or 48 h before the withdrawal testing.”