Abstract
Dipyrone analgesia in mice was potentiated by physostigmine, neostigmine and pilocarpine. This potentiation was antagonized by atropine sulfate and atropine methyl nitrate. Tremorine and dextroamphetamine which implicate brain monoamines in their analgesic effects, were inactive, as were carbachol and nicotine. Hydroxyzine did not potentiate dipyrone analgesia, ruling out a CNS depressant component in dipyrone potentiation. It was concluded that dipyrone which has central analgesic (Ruhnau, 1951) and parasympathomimetic effects (Lindner, 1956) is specifically potentiated by cholinergic drugs. Such potentiation of a non-narcotic analgesic by cholinergic agents argues against a specific involvement of cholinergic receptors in narcotics analgesia (and/or other narcotics' actions) and may indicate a cholinergic involvement in pain mechanisms and/or central analgesic effects without specific reference to narcotics.
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References
Beleslin, D., Polak, R. L.: Depression by morphine and chloralose of acetylcholine release from cat's brain. J. Physiol. (Lond.) 177, 411–419 (1965).
Bernheim, F., Bernheim, M. L. C.: Action of drugs on the cholinesterase of the brain. J. Pharmacol. exp. Ther. 57, 427–436 (1936).
Bianchi, C., Franceschini, J.: Experimental observations on Haffner's method for testing analgesic drugs. Brit. J. Pharmacol. 9, 280–284 (1954).
Cox, B. M., Weinstock, M.: The effect of analgesic drugs on the release of acetylcholine from electrically stimulated guinea pig ileum. Brit. J. Pharmacol. 27, 81–92 (1966).
Dole, V. P.: Biochemistry of addiction. Ann. Rev. Biochem. 39, 821–838 (1970).
Grewal, R. S.: A method for testing analgesics in mice. Brit. J. Pharmacol. 7, 433–437 (1952).
Harris, L. S.: Central neurohumoral systems involved with narcotic agonists and antagonists. Fed. Proc. 29, 28–32 (1970).
—, Dewey, W. L., Howes, J. F., Kennedy, J. S., Pars, H.: Narcotic antagonist analgesics: Interactions with cholinergic systems. J. Pharmacol. exp. Ther. 169, 17–22 (1969).
Hoffmeister, F., Kroneberg, G.: Experimental studies in animals on the differentiation of analgesic activity, pp. 270–277. In: Methods in drug evaluation. Ed.: P. Mantegazza and F. Piccinini. Amsterdam: Publ. North Holland, Publ. 1966.
Howes, J. F., Harris, L. S., Dewey, W. L., Voyda, C. A.: Brain acetylcholine levels and inhibition of the tail flick reflex in mice. J. Pharmacol. exp. Ther. 169, 23–28 (1969).
Ireson, J. D.: A comparison of the antinociceptive actions of cholinomimetic and morphine like drugs. Brit. J. Pharmacol. 40, 92–110 (1970).
Izquierdo, I., Izquierdo, J. A.: Effects of drugs on deep brain centers. Ann. Rev. Pharmacol. 21, 189–208 (1971).
Jaffe, J. H.: Narcotic analgesics, Chapter 15, pp. 237–273. In: The Pharmacological Basis of Therapeutics. Ed. L. S. Goodman and A. Gilman. New York: Publ. Macmillan & Co. 1970.
Johannesson, T.: The concentrations of morphine in the brains of rats receiving morphine and neostigmine. Acta pharmacol. (Kbh.) 19, 286–292 (1962).
Krohs, W.: Pyrazole derivatives, Chapter 7, pp. 331–403. In: Analgetics. Ed. G. DeStevens. Medicinal Chem. monogr., vol. 5. New York: Publ. Academic Press 1965.
Lindner, E.: Experimental studies on the action of a pyrazolone derivative on smooth muscle organs. Arzneimittel-Forsch. 6, 124–127 (1956).
Litchfield, J. T., Wilcoxon, F.: A simplified method of evaluating dose effect experiments. J. Pharmacol. exp. Ther. 96, 99–113 (1949).
Martin, W. R.: Pharmacological redundancy as an adaptive mechanism in the central nervous system. Fed. Proc. 29, 13–18 (1970).
Melzack, R., Wall, P. D.: Interaction of fast and slow conducting fibre systems involved in pain and analgesia. Proc. 3rd Int. Pharm. Meet., vol. 9, pp. 231–242 (1966).
Metys, J. N., Wagner, N., Metysova, J., Berz, A.: Studies on the central antinociceptive action of cholinomimetic agents. Int. J. Neuropharm. 8, 413–425 (1969).
Naik, S. R.: Unpublished data (1971).
Ruhnau, D.: Die Wirkung des Novalgins auf das autonome Nervensystem. Diss., Univ. of Hanover 1951.
Sethy, V. H., Naik, S. R., Sheth, U. K.: The effect of drugs influencing amine synthesis on the analgesic action of tremorine. Psychopharmacologia (Berl.) 19, 73–80 (1971).
Szerb, J. C.: Interaction of cholinesterase inhibitors with morphine and levallorphan. Arch. int. Pharmacodyn. 111, 314–321 (1957).
Veldstra, H.: Synergism and potentiation with special reference to the combination of structural analogues. Pharmacol. Rev. 8, 339–387 (1956).
Weller, C. P., Ibrahim, I., Sulman, F. G.: Analgesic profile of tranquillizers in multiple screening tests in mice. Arch. int. Pharmacodyn. 176, 176–192 (1968).
Wilson, A. E., Domino, E. F.: Inhibitory effects of morphine on brain acetylcholine depletion following intraventricular hemicholinium. Pharmacologist 12, 294 (1970).
Woolf, G., MacDonald, A. D.: The evaluation of the analgesic action of pethidine hydrochloride (Demerol). J. Pharmacol. exp. Ther. 80, 300–307 (1944).
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Pharmacological Research Unit, Council of Scientific and Industrial Research, at the Department of Pharmacology.
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Kamat, U.G., Pradhan, R.J. & Sheth, U.K. Potentiation of a non-narcotic analgesic, dipyrone, by cholinomimetic drugs. Psychopharmacologia 23, 180–186 (1972). https://doi.org/10.1007/BF00401193
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DOI: https://doi.org/10.1007/BF00401193