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Nitrendipine decreases benzodiazepine withdrawal seizures but not the development of benzodiazepine tolerance or withdrawal signs
Author(s) -
Dolin S.J.,
Patch T.L.,
Rabbani M.,
Siarey R.J.,
Bowhay A.R.,
Little H.J.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14142.x
Subject(s) - flurazepam , nitrendipine , benzodiazepine , nimodipine , pharmacology , inverse agonist , midazolam , kindling , anesthesia , agonist , physical dependence , medicine , morphine , calcium , receptor , stimulation , sedation
1 The effects of the calcium channel blocking agent, nitrendipine, were studied on seizures in mice produced during withdrawal from chronic benzodiazepine treatment and on the development of tolerance to benzodiazepines. 2 Nitrendipine produced a dose‐dependent decrease in seizure incidence, when seizures were produced by the partial inverse agonist FG7142 during withdrawal from seven days treatment with flurazepam. 3 Nitrendipine did not raise the seizure thresholds in naïve mice to the full inverse agonist methyl‐6,7‐dimethoxy‐4‐ethyl‐β‐carboline‐3‐carboxylate (DMCM), or to the γ‐aminobutyric acid (GABA) antagonist, bicuculline. 4 When given concurrently with flurazepam for seven days, nitrendipine did not affect the incidence of seizures during flurazepam withdrawal. 5 When given concurrently with the benzodiazepines, nitrendipine did not prevent the development of tolerance to midazolam general anaesthesia or tolerance to the ataxic actions of flurazepam or midazolam. 6 Chronic treatment with flurazepam for seven days did not affect the K d or B max of [ 3 H]‐nimodipine binding in mouse whole brain or cerebral cortex. 7 These results with benzodiazepines are partially in contrast with those for ethanol, where nitrendipine not only decreased ethanol withdrawal seizures when given acutely, but also prevented the development of tolerance and withdrawal signs when given concurrently with ethanol. However, they do confrm the selectivity of nitrendipine for withdrawal‐induced seizures.