Prevention of Ethanol Withdrawal Seizures in Mice by Local Anesthetics and Dextro-Propranolol
It has been previously reported from this laboratory that the systemic administration of nonsedative doses of the local anesthetic lidocaine (Xylocaine®; Astra Pharmaceutical Products, Inc., Worcester, Mass.) prevents ethanol withdrawal seizures in mice (Freund, 1973b). Lidocaine, however, is rapidly metabolized and is not effective orally as a cardiac antiarrhythmic agent. The β-adrenergic blocking drug d-,l-propranolol (Inderal®; Ayerst Laboratories, New York, N.Y.), a racemic mixture containing equal proportions of dextro- (d-) and levo- (l-) propranolol, has a local anesthetic potency approximately equal to lidocaine (Morales-Aguilera and Williams, 1965). In contrast to lidocaine, however, propranolol is orally absorbable and has a much longer duration of action. Both the d- and the l- optical isomers of propranolol have the same local anesthetic potency, but d-propranolol has less than 1/100 the β-adrenergic blocking potency of the l- form (Barrett and Cullum, 1968). Therefore, it appears theoretically possible to take advantage of the long-lasting local anesthetic effect and oral absorbability of d-propranolol with its nearly absent β-adrenergic blocking properties.
KeywordsOptical Isomer Alcohol Withdrawal Syndrome Withdrawal Sign Ethanol Withdrawal Drinking Tube
Unable to display preview. Download preview PDF.
- Evans, G. H., and Shand, D. G. Disposition of propranolol. V. Drug accumulation and steady-state concentrations during chronic oral administration in men. Clin. Pharmacol. Ther., 14:487–493, 1973.Google Scholar
- Evans, G. H., Wilkinson, G. R., and Shand, D. G. The disposition of propranolol. IV. A dominant role for tissue uptake in the dose-dependent extraction of propranolol by the perfused rat liver. J. Pharmacol. Exp. Ther., 186:447–454, 1973.Google Scholar
- Freund, G. Alcohol, barbiturate, and bromide withdrawal syndromes in mice. In N. K. Mello and J. H. Mendelson (Eds.), Recent Advances in Studies of Alcoholism, Washington, D.C., U. S. Government Printing Office, pp. 453–471.Google Scholar
- Freund, G. Animal models of alcohol withdrawal syndromes and their relevance to pharmacology. In H. D. Cappel and A. E. LeBlanc (Eds.), Biological and Behavioral Approaches to Drug Dependence, Toronto, Addiction Research Foundation, pp. 13–25, 1975b.Google Scholar
- Hill, M. W., and Bangham, A. D. General depressant drug dependency: a biophysical hypothesis. In M. M. Gross (Ed.), Alcohol Intoxication and Withdrawal. Experimental Studies. II, pp. 1–9, New York, Plenum Press, 1975.Google Scholar
- Morales-Aguilera, A., and Williams, E. M. V. The effects on cardiac muscle of β-receptor antagonists in relation to their activity as local anesthetics. Br. J. Pharmacol., 24: 332–338, 1965.Google Scholar
- Morelli, H. F. Propranolol. Ann. Intern. Med., 78:913–917, 1973.Google Scholar
- Mullins, L. J. Anesthetics. In A. Lajtha (Ed.), Handbook of Neurochemistry, Vol VI, New York, Plenum Press, pp. 395–421, 1971.Google Scholar
- Rahn, K. H., Hawlina, A., Kersting, F., and Planz, G. Studies on the antihypertensive action of the optical isomers of propranolol in man. Psychopharmacologia, 286:319–323, 1974.Google Scholar
- Saelens, D. A., Walle, T., Privitera, P. J., et al. Central nervous system effects and metabolic disposition of a glycol metabolic of propranolol. J. Pharmacol. Exp. Ther., 188:86–92, 1974.Google Scholar
- Seeman, P. The membrane actions of anesthetics and tranquillizers. Pharmacol. Rev., 24:583–655, 1972.Google Scholar
- Zil, D. H., Sellers, E. M., McLeod, S. M., and Degani, N. Propranolol effect on tremor in alcoholic withdrawal. Ann. Intern. Med. 83:234–236, 1975.Google Scholar