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Studies on the central effects of bulbocapnine

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In the present investigation the central effects of bulbocapnine were studied. In mice and rats, the antagonism and synergism on the part of various substances on bulbocapnine catalepsy were investigated, together with the influence of the drug on the EEG in animals with chronically implanted electrodes.

In mice and rats, three types of drugs proved to be effective in attenuating the bulbocapnine-induced catalepsy: antihistaminics (diphenhydramine, promethazine), antiparkinsonians (amantadine, trihexyphenidyl), and antidepressives (imipramine). Potentiation in both intensity and duration of catalepsy was noted after administration of l-DOPA and 5-HTP. In rabbits, all the components of the cataleptic syndrome were much less marked than in the other animal species. Cats proved to be the most sensitive animal, the smallest effective dose of bulbocapnine being 5 mg/kg, s.c.

A biphasic effect of bulbocapnine was demonstrated in the experiments involving concomitant observations of EEG and behavior. In none of the animal species used were significant alterations of the cerebral electrical activity observed during the cataleptic state. In mice and rats, spikes appeared in the EEG only after the onset of immobility and they anticipated the excitatory phase.

Some of the described effects are interpreted as the results of an influence of the alkaloid on the central catecholaminergic system.

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  1. Alema', G., Sergio, C.: On the influence of some pharmacological substances upon the experimental catatonia produced by bulbocapnine, reserpine and chlorpromazine in rats. In: Psychotropic Drugs, pp. 168–170. S. Garattini and V. Ghetti, edit. Amsterdam: Elsevier 1957.

  2. Andèn, N. E., Butcher, S. G., Corrodi, H., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970).

  3. Boissier, J. R., Simon, P.: Un test simple pour l'étude quantitative de la catatonie provoquée chez le rat par les neuroleptiques. Application à l'étude des anticatatoniques. Thérapie 18, 1257–1277 (1963).

  4. Borenstein, P., Gekière, F., Aleonard, P., Gruet-Masson, J., Allègre, G.: Etude neurophysiologique de l'action psychomotrice d'une drogue: a propos de la catatonie bulbocapnique. Sem. Hôp. Paris 45, 1247–1257 (1969).

  5. Carlini, E. A., Sampaio, M. R. P., Santos, M., Carlini, G. R. S.: Potentiation of histamine and inhibition of diamine-oxidase by catatonic drugs. Biochem. Pharmacol. 14, 1657–1663 (1965).

  6. Carlsson, A., Lindqvist, M.: In vivo decarboxylation of α-methyl-DOPA and α-methylmetatyrosine. Acta physiol. scand. 54, 87–94 (1962).

  7. Chapman, J. E., Walaszek, E. J.: Inhibition of diamine oxidase by bulbocapnine. Biochem. Pharmacol. 11, 205–210 (1962).

  8. Coyle, J. T., Snyder, S. H.: Antiparkinsonian drugs: inhibition of dopamine uptake in the corpus striatum as a possible mechanism of action. Science 166, 899–901 (1969).

  9. Crossland, J., Woodruff, G. N., Woodruff, J. H.: The histamine content of brain during bulbocapnine-induced catalepsy. Life Sci. 5, 193–197 (1966).

  10. Ernst, A. M.: The role of biogenic amines in the extrapyramidal system. Acta physiol. pharmacol. neerl. 15, 141–154 (1969).

  11. Florio, V., Longo, V. G.: Neuroleptic drugs and the central dopaminergic system. Antagonism between L-DOPA and some butyrophenones on the EEG and motor effects due to stimulation of the mesencephalon in the rabbit. Neuropharmacology 10, 45–54 (1971).

  12. Grelak, R. P., Clark, R., Stump, J. M., Vernier, V. G.: Amantadine-dopamine interaction: possible mode of action in Parkinsonism. Science 169, 203–204 (1970).

  13. Hayle, T. J., McCormick, W. G.: Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Brit. J. Pharmacol. 12, 12–15 (1957).

  14. Halushka, P. V., Hoffmann, P. C.: Does tetrahydropapaveroline contribute to the cardiovascular actions of dopamine? Biochem. Pharmacol. 17, 1873–1880 (1968).

  15. Hess, S. M., Connamacher, R. H., Ozaki, M., Udenfriend, S.: The effects of α-methyl-DOPA and α-methylmetatyrosine on the metabolism of norepinephrine and serotonin in vivo. J. Pharmacol. exp. Ther. 134, 129–138 (1961).

  16. Holtz, P., Stock, K., Westermann, E.: Formation of tetrahydropapaveroline from dopamine in vitro. Nature (Lond.) 203, 656–658 (1964).

  17. Koella, W. R., Feldstein, A., Czicman, J. S.: The effects of para-chlorophenylalanine on the sleep of cats. Electroenceph. clin. Neurophysiol. 25, 481–490 (1968).

  18. Loizzo, A.: Correlati elettroencefalografici dell'azione di alcuni farmaci psicotropi sul topo (Mus Musculus L.) libero non anestetizzato. II. EEG e comportamento nel topo trattato con farmaci anticolinergici. Studi sassaresi 47, (suppl.) 72–91 (1969).

  19. Longo, V. G.: Action de la chlorpromazine, de la lévomepromazine et de la prochlorpémazine sur l'activité électrique cérébrale et sur le comportement du lapin. Electroenceph. clin. Neurophysiol. 12, 693–704 (1960).

  20. —, Florio, V.: Effects of neuroleptic drugs on the cerebral electrical activity of laboratory animals. Presentation of a model design for neuropharmacological experiments. Acta psychiat. belg. 70, 676–687 (1970).

  21. Morpurgo, C.: Effects of antiparkinson drugs on a phenothiazine-induced catatonic reaction. Arch. int. Pharmacodyn. 137, 84–90 (1962).

  22. Passouant, P., Passouant-Fontaine, Th., Cadilhac, J.: Modifications de l'excitabilité du cortex et de diverses structures sous-corticales au cours de la catalepsie provoquée par la bulbocapnine chez le chat. C. R. Biol. Soc. (Paris) 149, 2185 to 2187 (1955).

  23. Rogers, K. J., Slater, P.: Brain acetylcholine and monoamines during experimental catatonia. J. Pharm. Pharmacol. 23, 135–137 (1971).

  24. Scatton, B., Cheramy, A., Besson, M. J., Glowinsky, J.: Increased synthesis and release of dopamine in the striatum of the rat after amantadine treatment. Europ. J. Pharmacol. 13, 131–133 (1970).

  25. Schildkraut, J. J., Davis, J. M., Klerman, G. L.: Biochemistry of depressions. In: Psychopharmacology, pp. 625–648. D. H. Efron, ed. Washington: Public Health Service Publication 1968.

  26. Simon, P., Chermat, R., Larousse, C., Boissier, J. R.: Action de la bulbocapnine sur quelques tests de psychopharmacologie. Thérapie 25, 939–949 (1970).

  27. —, Langwinski, R., Boissier, J. R.: Comparaison de différents tests d'évaluation de la catalepsie chez le rat. Thérapie 24, 985–995 (1969).

  28. Spector, S., Sjoerdsma, A., Udenfriend, S.: Blockade od endogenous norepinephrine synthesis by α-methyltyrosine, an inhibitor of tyrosine hydroxylase. J. Pharmacol. exp. Ther. 147, 86–95 (1965).

  29. Stille, G.: Arousalhemmung und Katalepsie bei Neuroleptica. Arzneimittel-Forsch. 16, 255–256 (1966).

  30. —, Sayers, A.: Concerning the effect of bulbocapnine on the caudate loop. Experientia (Basel) 23, 1028–1029 (1967).

  31. Sulser, F., Watts, J., Brodie, B. B.: On the mechanism of antidepressant action of imipramine like drugs. Ann. N. Y. Acad. Sci. 96, 279–288 (1962).

  32. Szekely, E. G., Spiegel, E. A.: The effect of bulbocapnine upon the spontaneous electric activity of the brain and its reactivity to afferent stimuli. Electroenceph. clin. Neurophysiol. 6, 213–219 (1954).

  33. Tseng, L. F., Walaszek, E. J.: Influence of alteration of catecholamine and serotonin levels on bulbocapnine-induced catatonia. Pharmacologist 12, 198 (1970).

  34. Waada, J. A.: Behavioral and electrographic effects of intraventricular injection of bulbocapnine and other substances in freely moving monkeys. Ann. N. Y. Acad. Sci. 96, 227–250 (1962).

  35. Walsh, M. J., Davies, V. E., Yamanaka, Y.: Tetrahydropapaveroline: an alkaloid metabolite of dopamine in vitro. J. Pharmac. exp. Ther. 174, 388–400 (1970).

  36. Zetler, G.: Anticataleptic actions of amantadine hydrochloride. Naunyn-Schmiedebergs Arch. Pharmak. 266, 276–278 (1970).

  37. —, Mahler, K., Daniel, F.: Versuche zu einer pharmakologischen Differenzierung kataleptischer Wirkungen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 238, 486–501 (1960).

  38. —, Moog, E.: Die Bulbocapnine-Katatonie, ihre Synergisten und Antagonisten. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 232, 442–458 (1958).

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Loizzo, A., de Carolis, A.S. & Longo, V.G. Studies on the central effects of bulbocapnine. Psychopharmacologia 22, 234–249 (1971). https://doi.org/10.1007/BF00401786

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  • Bulbocapnine
  • Motor Activity
  • Catecholamines
  • EEG