Summary
A single dose of α-hexachlorocyclohexane (α-HCH) induces tolerance to the convulsive action of pentetrazol. The increase in pentetrazol seizure threshold becomes significant 3 h after administration of 200 mg/kg α-HCH and reaches a maximum 12–24 h after pretreatment. The effect is shown to persist for about 9 days.
Pentetrazol concentrations in brain and other organs during the maximum of anticonvulsive activity of α-HCH were found to be uneffected in α-HCH pretreated animals.
There is a linear relationship between α-HCH content of the brain and the concentration of pentetrazol when generalized convulsions occur. Increase in α-HCH content of the brain is accompanied by a decrease in the sensitivity of the central nervous system for pentetrazol.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Brink, J. J., Cariglia, N., Stein, D. G., Galipeau, L. A.: Uptake of (14C) Pentylenetetrazol by developing rat brain. Brain Res. 19, 445–450 (1970).
Casrilevitz, Mira de, Engelhardt, E., Esberard, C. A.: Maturation of convulsogenic activity induced by leptazol in the albino rat. Brit. J. Pharmacol. 42, 31–42 (1971).
Chen, G., Ensor, Ch. R., Portman, R.: Anticonvulsant effects of certain CNS depressants in convulsions induced by strychnine metrazol or caffeine. Arch. int. Pharmacodyn. 104, 333–338 (1956).
Coper, H., Herken, H., Klempau, I.: Wirkungsverlust krampferzeugender Pharmaka durch Hexachlorcyclohexan. Naturwissenschaften 38, 69–70 (1951).
Dashputra, P. G., Sharma, M. L., Rajapurkar, M. V.: Modification of Metrazol induced convulsions in rats by adrenal cortical steroids. Arch. int. Pharmacodyn. 150, 483–488 (1964).
Ghazal, A., Koransky, W., Portig, J., Vohland, H.-W., Klempau, I.: Beschleunigung von Entgiftungsreaktionen durch verschiedene Insecticide. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 249, 1–10 (1964).
Hall, J. A., Nelson, R. B., Edlin, A. I.: Effects of temperature on convulsive liability of pentylenetetrazol, strychnine sulfate and thebaine hydrochloride. I. Pharmaceut. Sci. 56, 298–299 (1967).
Herken, H.: Eingriffe am Nervensystem mit Hexachlorcyclohexan. Arzneimittel-Forsch. 1, 356–359 (1951).
Herken, H., Kewitz, H., Klempau, I.: Wirkungsverluste von Krampfgiften durch Hexachlorcyclohexan. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 215, 217–230 (1952).
Hint, H. C., Richter, A. W.: A simple intravenous infusion technique for mice. Method and some Applications. Acta pharmacol. (Kbh.) 14, 153–157 (1958).
Ko, G. K. W., Hosein, E. A.: The metabolic fate of pentylenetetrazol in the rat. Canad. J. Physiol. Pharmacol. 49, 356–365 (1971).
Koransky, W., Magour, S., Noack, G., Schulte-Hermann, R.: Über den Einfluß induzierender Substanzen auf Fremdstoff-Oxydasen und andere Redoxenzyme der Leber. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 263, 281–296 (1969).
Koransky, W., Portig, J., Münch, G.: Resorption, Verteilung und Ausscheidung von α- und γ-Hexachlorcyclohexan. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 244, 564–575 (1963).
Koransky, W., Portig, J., Vohland, H.-W., Klempau, I.: Aktivierung von Mikrosomenenzymen durch Hexachlorcyclohexan-Isomere. Ihr Einfluß auf die Scillirosidvergiftung der Ratte. Naunyn-Schmiedebergs Arch exp. Path. Pharmak. 247, 61–70 (1964).
Loewe, S., Aldous, R. A., Fox, S. R., Johnson, D. G., Perkins, W.: Isobols of dose-effect relations in the combination of phenthylene-tetrazole and trimethadione. J. Pharmacol. exp. Ther. 113, 475–480 (1955).
Owens, G.: Effect of hypothermia on seizures induced by physical and chemical means. Amer. J. Physiol. 193, 560–562 (1958).
Portig, J., Koransky, W., Wahner-Roedler, D.: The Biotransformation of nikethamide in the rat and its acceleration by hexachlorocyclohexane. Naunyn-Schmiederberg's Arch. Pharmacol. 274, 154–170 (1972).
Segelova, J. V.: Age specific reactions of animals to the effect of cardiazol (metrazol) and hexenal (hexobarbital). Farmakol. i. Toksikol. 29, 404–406 (1966).
Seller, M. J., Spector, R. G.: Effect of aldosterone and cortisol on leptazol-induced seizures in rats. Brit. J. Pharmacol. 19, 271–273 (1962).
Swinyard, E. A.: The effect of experimentally induced stress on pentylenetatrezol seizure threshold in mice. Psychopharmacologia (Berl.) 4, 343–353 (1963).
Swinyard, E. A., Radhakrishnan, N., Goodman, L. S.: Effect of brief restraint on the convulsive threshold of mice. J. Pharmacol. exp. Ther. 138, 337–342 (1962).
Swinyard, A. E., Toman, J. E. P.: Effects of alterations in body temperature on properties of convulsive seizures in rats. Amer. J. Physiol. 154, 207–210 (1948).
Torda, C., Wolff, H. G.: Effects of various concentrations of adrenocorticotrophic hormone on Electrical activity of brain and on sensitivity to convulsion-inducing agents. Amer. J. Physiol. 168, 406–413 (1952).
Vohland, H.-W., Koransky, W.: Effect of α-Hexachlorocyclohexane on metabolism and excretion of Pentetrazol (cardiazol) in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 273, 99–108 (1972).
Withrow, C. D., Stout, R. J., Barton, L. J., Beacham, W. S., Woodbury, D. M.: Anticonvulsant effects of 5,5-demethyl-2,4-oxazolidinedione (DMO). J. Pharmacol. exp. Ther. 161, 335–341 (1968).
Author information
Authors and Affiliations
Additional information
Supported by Deutsche Forschungsgemeinschaft.
Rights and permissions
About this article
Cite this article
Vohland, H.W., Koransky, W. & Zufelde, H. Effect of α-hexachlorocyclohexane on the convulsive activity of pentetrazol (Cardiazol®) in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 289–298 (1972). https://doi.org/10.1007/BF00500057
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00500057