Summary
-
1.
The anticonvulsive potencies of diazepam, phenobarbital and baclofen against convulsions induced by oxygen under high pressure (OHP), by isoniazid and by strychnine were investigated in mice and rats.
-
2.
The anticonvulsive potency of diazepam was much higher than that of phenobarbital and baclofen against all three types of convulsions.
-
3.
The selective activity of diazepam against isoniazid induced convulsions in rats (dose ratio ED50 phenobarbital/ED50 diazepam: 400) could not be confirmed in mice (dose ratio ED50 phenobarbital/ED50 diazepam: 20–40), where diazepam was equipotent against all three types of convulsions.
-
4.
Baclofen which does not inhibit strychnine induced convulsions was equipotent in inhibiting convulsions evoked by isoniazid and OHP in mice.
-
5.
The results are in agreement with the postulated GABA-inhibitory mechanism of OHP induced convulsions, whereas they make a glycine inhibitory mechanism very unlikely. Although the results do not allow further conclusions about the mode of action of diazepam, a clinical trial of diazepam in OHP-induced convulsions should be considered.
Similar content being viewed by others
References
Bein, H. J.: Pharmakologische Differenzierung von Muskelrelaxantien aus: Aspekte der Muskelspastik von W. Birkmeyer, S. 76–82. Bern-Stuttgart-Wien: H. Huber 1972
Costa, E., Guidotti, A., Mao, C. C., Suria, A.: New concepts on the mechanism of action of benzodiazepines. Life Sci. 17, 167–186 (1975)
Diaz, M. P., Ngai, S. H.: The effect of oxygen on the turnover rate of biogenic amines in vivo. II. Serotonin. Fed. Proc. 26, 708 (1967)
Doteuchi, M., Costa, E.: Pentylenetetrazol convulsions and brain catecholamine turnover rate in rats and mice receiving diphenylhydantoin or benzodiazepines. Neuropharmacology 12, 1059–1072 (1973)
Faiman, M. D., Heble, A., Mehl, R. G.: HBO and brain norepinephrine and 5-hydroxtryptamine: Oxygen pressure interactions. Life Sci. 8, 1163–1178 (1969)
Faiman, M. D., Mehl, R. G., Myers, M. B.: Brain norepinephrine and serotonin in central oxygen toxicity. Life Sci. 10, 21–34 (1971)
Fernstrom, J. D., Shabshelowitz H., Faller, D. V.: Diazepam increases 5-hydroxyindole concentrations in rat brain and spinal cord. Life Sci. 15, 1577–1584 (1974)
Haefely, W., Kulcsar, A., Mohler, H., Pieri, L., Pole, P., Schafferer, R.: Possible involvement of GABA in the central action of benzodiazepines. Advances; Biochem. Psychopharmacol., vol. 14, (E. Costa and P. Greengard, eds.). New York: Raven Press 1975
Jenner, P., Chadwick, D., Reynolds, E. H., Marsden, C. D.: Altered 5-HT metabolism with clonazepam, diazepam and diphenylhydantoin. J. Pharm. Pharmacol. 27, 707–710 (1975)
Lidbrink, P., Corrodi, H., Fuxe, F.: Benzodiazepines and barbiturates: Turnover changes in central 5-hydroxytryptamine pathways. Europ. J. Pharmacol. 26, 35–40 (1974)
Litchfield, J. T., Wilcoxon, F.: A simplified method of evaluating dose-effect experiments. J. Pharmacol. exp. Ther. 96 99–113 (1949)
Mao, C. C., Guidotti, A., Costa, E.: Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action of diazepam. Naunyn-Schmiede-berg's Arch. Pharmacol. 289, 369–378 (1975)
Neff, N. H., Costa, E.: The effect of oxygen on the turnover rate of biogenic amines in vivo. I. Catecholamines. Fed. Proc. 26, 463 (1967)
Nicholl, R., Paddjen, A.: Pentylenetetrazol: an antagonist of GABA at primary afferents of the isolated frog spinal cord. Neuropharmacology 15, 69–71 (1976)
Paton, W. D. M.: Experiments on the convulsant and anaesthetic effects of oxygen. Brit. J. Pharmacol. Chemother. 29, 350–366 (1967)
Polc, P., Haefely, W.: Effect of two benzodiazepines, phenobarbitone and baclofen on synaptic transmission in the cat cuneate nucleus. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 121–131 (1976)
Radomski, M. W., Watson, W. J.: Effect of lithium on acute oxygen toxicity and associated changes in brain γ-aminobutyric acid. Aerosp. Med. 44, 387–392 (1973)
Saad, S. F.: Effect of diazepam on γ-aminobutyric acid (GABA) content of mouse brain. J. Pharm. Pharmacol. 24, 839–840 (1972)
Suria, A., Costa, E.: Action of diazepam, dibutyryl cGMP and GABA on presynaptic nerve terminals in bullfrog sympathetic ganglia. Brain Res. 87, 102–106 (1975)
Tunnicliff, G., Urton, M., Wood, J. D.: Susceptibility of chick brain l-glutamic acid decarboxylase and other neurotransmitter enzymes to hyperbaric oxygen in vitro. Biochem. Pharmacol. 22, 501–505 (1973)
Wood, J. D.: A possible role for gamma-aminobutyric acid in the homeostatic control of brain metabolism under conditions of hypoxia. Exp. Brain Res. 4, 81–84 (1967)
Wood, J. D.: Seizures induced by hyperbaric oxygen and cerebral γ-aminobutyric acid in chicks during development. J. Neurochem. 17, 573–579 (1970)
Wood, J. D.: The effect on GABA metabolism in brain of isonicotinic acid hydrazide and pyridoxine as a function of time after administration. J. Neurochem. 19, 1527–1537 (1972)
Wood, J. D., Peesker, S. J.: The role of GABA metabolism in the convulsant and anticonvulsant actions of aminooxyacetic acid. J. Neurochem. 20, 379–387 (1973)
Wood, J. D., Radomski, M. W., Watson, W. J.: A study of possible biochemical mechanisms involved in HBO-induced changes in cerebral γ-aminobutyric acid levels and accompanying seizures. Canad. J. Biochem. 49, 543–547 (1971)
Wood, J. D., Peesker, S. J., Rozdilsky, B.: Sensitivity of GABA synthesis in human brain to oxygen poisoning. Aviat. Space Environ. Med. 46, 1155–1156 (1975)
Yarmosh, D. F., Dash, H. H.: Catecholamine turnover rates in the rat brain after in vivo exposure to HBO. Clin. Chem. 21, 1027 (1975)
Young, A. B., Zukin, S. R., Snyder, S. H.: Interaction of benzodiazepines with central nervous glycine receptors: possible mechanism of action. Proc. nat. Acad. Sci. (Wash.) 71, 2246–2250 (1974)
Young, A., Snyder, S. H.: Strychnine binding associated with glycine receptors of the central nervous system. Proc. nat. Acad. Sci. (Wash.) 70, 2832–2836 (1973)
Author information
Authors and Affiliations
Additional information
A preliminary report was given at the Pharmacology Meeting at Mainz, March 23–26, 1976. E. Beubler and F. Lembeck, Naunyn-Schmiedeberg's Arch. Pharmacol. 293 R 14 (1976)
Rights and permissions
About this article
Cite this article
Lembeck, F., Beubler, E. Convulsions induced by hyperbaric oxygen: Inhibition by phenobarbital, diazepam and baclofen. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 47–51 (1977). https://doi.org/10.1007/BF00508809
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00508809