Abstract
Di-n-propylacetate (DPA), a drug known to increase brain γ-aminobutyric acid (GABA) levels and to inhibit GABA-transaminase (GABA-T) activity, was administered during the ethanol withdrawal period to rats made physically dependent upon ethanol. Under all conditions tested, 400 mg DPA/kg injected i.p. significantly reduced the withdrawal hyperexcitable state induced by acoustic stimulation. The effect was seen as early as 30 min after the administration of DPA and lasted for at least 2 hrs. Readministration of the same dose of DPA 6.5 hrs after its initial injection again mitigated withdrawal symptoms. A 200 mg/kg dose of DPA was significantly effective for only 1 hr after its administration. Neither dose led to mortality or observable tranquilization. The results suggest that DPA may be a useful agent in the control of the hyperexcitable state induced by ethanol withdrawal and that the GABA system may be involved in this state.
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Baxter, C. F., Roberts, E.: Elevation of γ-aminobutyric acid in brain: Selective inhibition of γ-aminobutyric-α-ketoglutaric acid transaminase. J. biol. Chem. 236, 3287–3294 (1961)
Carraz, G.: In: Pharmacodynamie de l'acide dipropylacetique (ou propyl-2-pentanoique) et de ses amides. Grenoble: Imprimerie Eymond 1968
Crossland, J., Turnbull, M. J.: Gamma-aminobutyric acid and the barbiturate abstinence syndrome in rats. Neuropharmacology 11, 733–738 (1972)
Elliot, K. A. C., van Gelder, N. M.: The state of factor I in rat brain: The effects of metabolic conditions and drugs. J. Physiol. (Lond.) 153, 423–432 (1960)
Essig, C. F.: Possible relation of brain gamma-aminobutyric acid (GABA) to barbiturate abstinence convulsions. Arch. int. Pharmacodyn. Ther. 176, 97–103 (1968)
Freund, G.: Alcohol withdrawal syndrome in mice. Arch. Neurol. (Chic.) 21, 315–320 (1969)
Freund, G.: The prevention of ethanol withdrawal seizures in mice by lidocaine. Neurology (Minneap.) 23, 92–94 (1973)
Godin, Y., Heiner, L., Mark, J., Mandel, P.: Effects of di-n-propylacetate, an anticonvulsive compounds, on GABA metabolism. J. Neurochem. 16, 869–873 (1969)
Goldstein, D. B.: Alcohol withdrawal reactions in mice: Effects of drugs that modify neurotransmission. J. Pharmacol. exp. Ther. 186, 1–9 (1973)
Goldstein, D., Pal, N.: Alcohol dependence produced in mice by inhalation of ethanol: Grading the withdrawal reaction. Science 172, 288–290 (1971)
Jeavons, P. N., Clark, J. E.: Sodium valproate in treatment of epilepsy. Brit. med. J. 1974II, 584–586
Killam, K. F., Bain, J. A.: Convulsant hydrazides I: In vitro and in vivo inhibition of vitamin B6 enzymes by convulsant hydrazides. J. Pharmacol. exp. Ther. 119, 255–262 (1957)
Kuriyama, K., Roberts, E., Rubenstein, M. K.: Elevation of gamma-aminobutyric acid in brain with amino-oxyacetic acid and susceptibility to convulsive seizures in mice: A quantitative re-evaluation. Biochem. Pharmacol. 15, 221–236 (1966)
Leberton, S., Carraz, G., Meunier, H., Beriel, H.: Propriétés pharmacodynamiques de l'acide N-dipropylacétique. Deuxième mémoire sur les propriétés antileptiques. Thérapie 19, 451–476 (1964)
Lieber, C. S., DeCarli, L. M.: Ethanol dependence and tolerance: A nutritionally controlled experimental model in the rat. Res. Commun. Chem. Path. Pharmacol. 6, 983–991 (1973)
Maitre, L., Ciesielski, L., Mandel, P.: Effect of 2-methyl 2-ethyl caproic acid and 2-2-dimethyl valeric acid on audiogenic seizures and gamma aminobutyric acid. Biochem. Pharmacol. 23, 2363–2368 (1974)
Majchrowicz, E.: Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia (Berl.) 43, 245–254 (1975)
Meunier, H., Carraz, G., Meunier, Y., Eymard, P., Airmard, M.: Propriétés pharmacodynamique de l'acide n-dipropylacétique. Thérapie 18, 435–438 (1963)
Noble, E. P., Tewari, S.: Metabolic aspects of alcoholism in the brain. In: Metabolic aspects of alcoholism, C. S. Lieber, ed. Lancaster, England: Medical and Technical Publishing Co., Ltd. (in press, 1975)
Purpura, D. P., Girado, M., Smith, T. G., Gomez, J. A.: Synaptic effects of systemic γ-amino butyric acid in cortical regions of increased vascular permeability. Proc. Soc. exp. Biol. (N. Y.) 97, 348–353 (1958)
Roberts, E., Kuriyama, K.: Biochemical-physiological correlations in studies of the γ-aminobutyric acid system. Brain Res. 8, 1–35 (1968)
Siegel, S.: Nonparametric statistics for the behavioral sciences. New York: McGraw-Hill 1956
Simler, S., Ciesielski, L., Maitre, M., Randrianarisoa, H., Mandel, P.: Effect of sodium n-dipropylacetate on audio-genic seizures and brain γ-aminobutyric acid level. Biochem. Pharmacol. 22, 1701–1708 (1973)
Simler, S., Randrianarisoa, H., Lehmann, A., Mandel, P.: Effects du di-n-propylacétate sur les crises audiogènes de la souris. J. Physiol. (Paris) 60 (Suppl. 2), 547 (1968)
Simler, S., Randrianarisoa, H., Lehmann, A., Mandel, P.: In: Pathogenesis of epilepsy. G. Usunoff, E. Atsev, I. Dosseva, and S. Dimov, eds., pp. 59–70. Sofia: Publishing House of the Bulgarian Academy of Sciences 1971
Völzke, E., Doose, H.: Epilepsia. J. Internat. League against Epilepsy 14, 185 (1973)
Wallgren, H., Kosunen, A.-L., Ahtee, L.: Technique for producing an alcohol withdrawal syndrome in rats. Israel J. med. Sci. 9 (Suppl.), 63–71 (1973)
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Noble, E.P., Gillies, R., Vigran, R. et al. The modification of the ethanol withdrawal syndrome in rats by Di-n-propylacetate. Psychopharmacologia 46, 127–131 (1976). https://doi.org/10.1007/BF00421381
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DOI: https://doi.org/10.1007/BF00421381