Abstract
The calcium antagonists nimodipine and dantrolene were compared with diazepam in an animal model of tolerance and physical dependence upon ethanol. Nimodipine and dantrolene were both effective in suppressing withdrawal tremors but diazepam was clearly superior to both agents. These results suggest that the ethanol with-drawal syndrome is only partially mediated by increased calcium flux.
Similar content being viewed by others
References
Belleman P, Schade A, Towart R (1983) Dihydropyridine receptor in rat brain labelled with 3H-nimodipine. Proc Natl Acad Sci USA 80:2356–2360
Dolin SJ, Little PJ (1986) Augmentation by calcium channel antagonists of general anaesthetic potency in mice. Br J Pharmacol 87:40P
Dolin S, Little H, Hudspith M, Pagonis C, Littleton J (1987) Increased dihydropydrine-sensitive calcium channels in rat brain may underlie ethanol physical dependence. Neuropharmacology 26:275–279
Hoffmeister F, Benz U, Heise A, Krause HP, Neuser V (1982) Behavioral effects of nimodipine in animals. Arzneimittelforschung 32:347–360
Isaacson RL, Molina JC, Draski LJ, Johnston JE (1985) Nimodipine's interaction with other drugs: 1. Ethanol. Life Sci 36:2195–2199
Kanda K, Flaim SF (1986) Effects of nimodipine on cerebral blood flow in conscious rat. J Pharmacol Exp Ther 236:41–47
Kroal GJ, Lettieri JT, Mazzu AL, Burkholder DE, Birkett JP, Taylor RJ, Bon C (1987) Bioequivalence of different nitrendipine tabled dosage formulations. J Cardiovasc Pharmacol [Suppl 4] 9:5129–5135
Little HJ, Dolin SJ, Halsey MJ (1986) Calcium antagonists decrease the ethanol withdrawal syndrome. Life Sci 39:2059–2065
Lowry OH, Rosebrough NJ, Farr AC, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:4119–4125
Lynch MA, Littleton JM (1983) Possible association of alcohol tolerance with increased synaptic Ca+ sensitivity. Nature 303:175–176
Majchrowicz E (1975) Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia 43:245–254
Majchrowicz E, Hunt WA, Piantadosi C (1976) Suppression by 1,3-butanediol of the ethanol withdrawal syndrome in rats. Science 194:1181–1182
Peroutka SJ, Allen GS (1983) Calcium channel antagonist binding sites labelled by 3H-nimodipine in human brain. J Neurosurg 59:933–937
Sanguinetti MC, Kass RS (1984) Voltage-dependent block of calcium channel current in the calf purkinje fiber by dihydropyridine calcium channel antagonists. Circ Res 55:336–348
Stokes JA, Harris RA (1982) Alcohols and synaptosomal calcium transport. Mol Pharmacol 22:99–104
Winquist RJ (1984) Modulators of intracellular calcium. Drug Dev Res 4:241–256
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bone, G.H.A., Majchrowicz, E., Martin, P.R. et al. A comparison of calcium antagonists and diazepam in reducing ethanol withdrawal tremors. Psychopharmacology 99, 386–388 (1989). https://doi.org/10.1007/BF00445563
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00445563