Effects of dihydropyridine calcium channel antagonists in ethanol withdrawal; doses required, stereospecificity and actions of Bay K 8644.
The effects of dihydropyridine calcium channel antagonists, and the calcium channel activator, Bay K 8644, were examined on the convulsive behaviour induced by handling in mice following withdrawal from chronic ethanol inhalation. Nimodipine and nitrendipine and PN 200-110 significantly decreased the convulsive behaviour, after intraperitoneal doses of the same order of magnitude as have been found by others to be required for displacement of radiolabelled dihydropyridine in the CNS. The (+) isomer of PN 200-110 was effective, but the (-) isomer, which is ineffective in vitro, had no significant action. Bay K 8644 prevented the actions of nimodipine against the ethanol withdrawal syndrome. The behavioural ratings after nimodipine plus Bay K 8644 were significantly higher than after vehicle treatment. Bay K 8644 alone, when given to naive mice, caused convulsive behaviour resembling that seen in withdrawal from chronic ethanol treatment, but when given during ethanol withdrawal did not significantly increase the behavioural signs.
Littleton
J M
JM
Department of Pharmacology, Kings College, London, UK.
Little
H J
HJ
Whittington
M A
MA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000627:therapeutic use*; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D017275:Isradipine; D008297:Male; D051379:Mice; D009553:Nimodipine / Q000008:administration & dosage / Q000627:therapeutic use; D009568:Nitrendipine / Q000008:administration & dosage / Q000627:therapeutic use; D010069:Oxadiazoles / Q000627:therapeutic use; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology; D013997:Time Factors
D002121:Calcium Channel Blockers; D010069:Oxadiazoles; D000431:Ethanol; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D017275:Isradipine