Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies with ethanol have indicated that dihydropyridine-sensitive calcium (Ca++) channels may be involved in the adaptation to prolonged exposure to ethanol. This study investigated the effects, in mice, of the dihydropyridine Ca++ antagonist, nitrendipine, on acute tolerance to nitrous oxide after 60 min exposure to anesthetizing concentrations, and also the withdrawal syndrome which occurred following removal from nitrous oxide. Control mice were anesthetized by nitrous oxide concentrations in the range 1.28-1.51 atmospheres. Nitrendipine 10, 50, and 100 mg.kg-1, i.p., produced a dose-dependent potentiation of nitrous oxide anesthesia (P less than 0.05 for nitrendipine 50 and 100 mg.kg-1). Tolerance to nitrous oxide anesthesia developed over 60 min (13% increase in ED50, P less than 0.05). Concurrent administration of nitrendipine at all doses prevented the development of nitrous oxide tolerance. After 60 min exposure to nitrous oxide 1-1.5 atmospheres, all control mice showed handling seizures. Nitrendipine diminished or prevented nitrous oxide withdrawal seizures, in a dose-dependent manner (P less than 0.05 for nitrendipine 50 and 100 mg.kg-1). These results support the importance of the role of dihydropyridine-sensitive Ca++ channels in the mechanism of tolerance and dependence to central depressant drugs. They also suggest that acute and chronic tolerance to sedative drug action may share some common pathways, and that tolerance and physical dependence may share a common mechanism through voltage-operated Ca++ channels.
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PMID:Effects of "nitrendipine" on nitrous oxide anesthesia, tolerance, and physical dependence. 252 37

We have shown previously that the dihydropyridine calcium channel antagonist nitrendipine, given chronically, prevents the development of ethanol tolerance and physical dependence. The present study examines the effects on barbiturate tolerance and physical dependence. Nitrendipine, given acutely during withdrawal, provided little protection against barbiturate withdrawal, as measured by convulsive behaviour on handling. When nitrendipine was given chronically concurrently with the barbiturate, a prolonged protection against the withdrawal syndrome was seen. Acute nitrendipine significantly increased the latency of seizures in response to the partial benzodiazepine inverse agonist FG7142 during barbiturate withdrawal, but there was no effect on the seizure incidence in response to bicuculline. Chronic treatment with nitrendipine did not alter the development of tolerance to the ataxic or general anaesthetic actions of barbiturates, but evidence was found of a possible interaction between nitrendipine and pentobarbitone, which may have been pharmacokinetic. The results suggest that neuronal calcium channels may be involved to some degree in the development of the changes responsible for barbiturate withdrawal, but to a less extent than found previously for ethanol dependence.
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PMID:Dihydropyridine-sensitive calcium channels and barbiturate tolerance and withdrawal. 820 88