Summary
We have studied the interactions of reserpine and the monoamine oxidase inhibitors, nialamide and isocarboxazid, in rabbits. EEG recordings were made from animals with acute and chronically implanted electrodes. Gross behavioral observations were made in freely moving rabbits and brain amine concentrations of norepinephrine and serotonin were also determined. Emphasis was placed on observing drug effects over periods of time ranging up to 13 days. Rabbits given isocarboxazid or nialamide alone exhibit a phenomenon rarely seen in the control animals, namely partial activation, an EEG pattern in which slow waves of high amplitude are maintained in the cortex while fast activity appears in subcortical structures. This effect was also observed in rabbits treated with nialamide and reserpine in combination. By appropriate dosage schedules in which reserpine was administered to animals pretreated with monoamine oxidase inhibitors it was possible to maintain extended periods of frank arousal or EEG activation over a period of several days. The absolute concentrations of brain amines bore little or no relationship to the EEG effects observed, however, increased ratios of serotonin to norepinephrine were observed in conjunction with EEG activation and signs of behavioral excitement.
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References
Axelrod, J.: Metabolism and inactivation of noradrenaline and adrenaline and the effect of drugs. Pharmacology of Cholinergic and Adrenergic Transmission (Koelle, Douglas and Carlsson, Eds.) Pergamon Press and Czechoslovak Medical Press, 205–220 (1965).
Bessendorf, H., F. A. Steiner u. A. Hurlimann: „Laroxyl“ ein neues Antidepressivum mit sedierender Wirkung. Schweiz, med. Wschr. 92, 244–246 (1962).
Bunney, W. E., and J. M. Davis: Norepinephrine in depressive reactions. Arch. gen. Psychiat. 13, 483–494 (1965).
Chessin, M., E. R. Kramer, and C. C. Scott: Modifications of the pharmacology of reserpine and serotonin by iproniazid. J. Pharmacol. exp. Ther. 119, 453–460 (1957).
Corrodi, H.: Blockade of the psychotic syndrome caused by nialamide in mice. J. Pharm. Pharmacol. 18, 197–198 (1966).
Costa, E., G. R. Pscheidt, W. G. van Meter, and H. E. Himwich: Brain concentration of biogenic amines and EEG patterns of rabbits. J. Pharmacol. exp. Ther. 130, 81–88 (1960).
DeCastro, G., and P. Mundeleer: Symposium on Neuroleptanalgesia, First European Congress of Anesthesiology, Vienna Sept. 5 (1962).
Eidelberg, E., M. K. Miller, and M. Long: Spectrum analysis of electroence-phalographic changes induced by some psychoactive agents. Their possible relationship to changes in cerebral biogenic amine levels. Int. J. Neuropharmacol. 5, 59–74 (1966).
Funderburk, W. H., K. F. Finger, A. B. Drakontides, and J. A. Schneider: EEG and biochemical findings with MAO inhibitors. Ann. N. Y. Acad. Sci. 96, 289–301 (1962).
Glowinski, J., and J. Axelrod: Effects of drugs on the disposition of H3-nor-epinephrine in the rat brain. Pharmacol. Rev. 18, 775–785 (1966).
Graeff, F. G., J. Garcia Leme, and M. Rochae Silva: Role played by catechol and indoleamines in the central actions of reserpine after monoaminoxidase inhibition. Int. J. Neuropharmacol. 4, 17–26 (1965).
Green, H., and R. W. Erickson: Further studies with tranylcypromine (monoamine oxidase inhibitor) and its interaction with reserpine in rat brain. Arch. int. Pharmacodyn. 135, 407–425 (1962).
—, and J. L. Sawyer: Intracellular distribution of norepinephrine in rat brain. I. Effect of reserpine and the monoamine oxidase inhibitors, trans-2-phenyl-cyclopropylamine and 1-isonicotinyl-2-isopropyl hydrazine. J. Pharmacol. exp. Ther. 129, 243–249 (1960).
Haggendal, J., and M. Lindqvist: Brain monoamine levels and behavior during long-term administration of reserpine. Int. J. Neuropharmacol. 3, 59–64 (1964).
Haskovec, L., and K. Rysanek: The action of reserpine in imipramine-resistent depressive patients. Psychopharmacologia (Berl.) 11, 18–30 (1967).
Hillarp, N. A., K. Fuxe, and A. Dahlstrom: Demonstration and mapping of central neurons containing dopamine, noradrenaline and 5-hydroxy tryptamine and their reactions to psychopharmaca. Pharmacol. Rev. 18, 727–742 (1966).
Himwich, H. E., and G. R. Pscheidt: Discussion — Working Group I. Neuro-psychopharmacology (Bente, and Bradley, Eds.), Vol. 4, pp. 38–42. Amsterdam: Elsevier Publishing Co. 1965.
Malmfors, T.: Studies on adrenergic nerves. Upsalla, Sweden: Almqvist and Wiksells 1965.
Mead, J. A. R., and K. F. Finger: A single extraction method for the determination of both norepinephrine and serotonin in brain. Biochem. Pharmacol. 6, 52–53 (1961).
Mendigutia, R. C., and J. L. L. Penasco: Psicofarmacologia de la Depression. Madrid: Editorial Pax Montalvo 1964.
Pscheidt, G. R., W. G. Steiner, and H. E. Himwich: An electroencephalographic and chemical reevaluation of the central action of reserpine in the rabbit. J. Pharmacol. exp. Ther. 144, 37–43 (1964).
Savoldi, F., A. Arrigo, L. Bolzani, and V. Cosi: Action électrophysiologique des substances antiaminoxydasiques. Schweiz. Arch. Neurol. Neurochir. Psychiat. 95, 271–319 (1965).
Sawyer, C. H., J. W. Everett, and J. D. Green: The rabbit diencephalon in stereotaxic coordinates. J. comp. Neurol. 101, 801–824 (1954).
Shore, P. A., and J. S. Olin: Identification and chemical assay of norepinephrine in brain and other tissues. J. Pharmacol. exp. Ther. 122, 295–300 (1958).
Spector, S., R. Kuntzman, P. A. Shore, and B. B. Brodie: Evidence for release of brain amines by reserpine in presence of monoamine oxidase inhibitors: implication of monoamine oxidase in norepinephrine metabolism in brain. J. Pharmacol. exp. Ther. 130, 256–261 (1960).
—, C. W. Hirsch, and B. B. Brodie: Association of behavioral effects of Pargyline, a non-hydrazide MAO inhibitor with increase in brain norepinephrine. Int. J. Neuropharmacol. 2, 81–93 (1963).
Stein, L., and O. S. Ray: Accelerated recovery from reserpine depression by monoamine oxidase inhibitors. Nature (Lond.) 188, 1199–1200 (1960).
Steiner, W. G., G. R. Pscheidt, E. Costa, and H. E. Himwich: Alpha-ethyl-tryptamine (etryptamine): an electroencephalographic, behavioral and neurochemical analysis. Psychopharmacologia (Berl.) 4, 354–366 (1963).
Sulser, F., J. Watts, and B. B. Brodie: On the mechanism of antidepressant action of imipramine-like drugs. Ann. N. Y. Acad. Sci. 96, 279–286 (1962).
Tissot, R.: Monoamines et Système Nerveux Central. Doctoral Thesis (Dain, Ed.) Paris 1961.
Wada, J. A., and E. G. McGeer: Central aromatic amines and behavior (III). Arch. Neurol. (Chic.) 14, 129–142 (1966).
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Fellow of the Conselho Nacional de Pesquisas, Rio de Janeiro, Brazil.
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Bueno, J.R., Pscheidt, G.R. & Himwich, H.E. Interactions of monoamine oxidase inhibitors and reserpine: an EEG, gross behavioral and biochemical analysis. Psychopharmacologia 12, 400–413 (1968). https://doi.org/10.1007/BF00401345
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DOI: https://doi.org/10.1007/BF00401345