Summary
The effects of amphetamine, metamphetamine, propylhexedrine, biperiden and atropine were studied in experiments on electroseizure threshold in rats. In high doses these drugs lowered the threshold of electroseizures and antagonized the threshold lowering produced by reserpine, with the exception of atropine, which enhanced the action of reserpine. Low doses of the drugs and combinations of low doses of metamphetamine, propylhexedrine and biperiden did not influence electroseizure threshold, but inhibited the action of reserpine. The effect of phenytoin on the threshold lowered by reserpine was enhanced by low doses of metamphetamine, propylhexedrine and biperiden. Tetrabenazine caused threshold lowering which was antagonized by metamphetamine, propylhexedrine, biperiden and atropine. Pretreatment with α-methyl-p-tyrosine, but not with diethyldithiocarbaminate abolished the effect of high doses of metamphetamine or propylhexedrine on the electroseizure threshold. Inhibition of the formation of DOPA or noradrenaline did not influence the action of reserpine or the antagonism between reserpine and the drugs of the amphetamine group. After a repeated injection of metamphetamine tachyphylaxis developed.
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Andén, N.-E., H. Corrodi, A. Dahlström, K. Fuxe, and T. Hökfelt: Effects of tyrosine hydroxylase inhibition on the amine levels of central monoamine neurones. Life Sci. 5, 561–568 (1966).
Arvidsson, J., I. Jurna, and G. Steg: Striatal and spinal lesions eliminating reserpine and physostigmine rigidity. Life Sci. 6, 2017–2020 (1967).
— B.-E. Roos, and G. Steg: Reciprocal effects on α- and γ-motoneurones of drugs influencing monoaminergic and cholinergic transmission. Acta physiol. scand. 67, 398–404 (1966).
Baird, J. R. C., and J. J. Lewis: Effects of drugs on noradrenaline and 3-hydroxytyramine (dopamine) levels and on the noradrenaline to dopamine ratio in the rat brain. Biochem. Pharmacol. 12, 579–581 (1963).
— — The effects of cocaine, amphetamine and some amphetamine-like compounds on the in vivo levels of noradrenaline and dopamine in the rat brain. Biochem. Pharmacol. 13, 1475–1482 (1964).
Bertler, Å.: Effect of reserpine on the storage of catecholamines in brain and other tissues. Acta physiol. scand. 51, 75–83 (1961).
Birkmayer, W., u. O. Hornykiewicz: Der L-3,4-Dihydroxyphenylalanin(=DOPA)-Effekt bei der Parkinson-Akinesie. Wien. klin. Wschr. 73, 787–788 (1961).
— — Der L-Dioxyphenylalanin (L-DOPA)-Effekt beim Parkinsonsyndrome des Menschen. Zur Pathogenese und Behandlung der Parkinson-Akinesie. Arch. Psychiat. Nervenkr. 203, 560–574 (1962).
— — Weitere experimentelle Untersuchungen über L-DOPA beim Parkinson-Syndrom und Reserpin-Parkinsonismus. Arch. Psychiat. Nervenkr. 206, 367–381 (1964).
Brodie, B. B., S. Spector, and P. A. Shore: Interaction of drugs with norepinephrine in the brain. Pharmacol. Rev. 11, 548–564 (1959).
Carlsson, A.: Evidence for a role of dopamine in extrapyramidal functions. Acta neuroveg. (Wien) 26, 484–493 (1964).
— Drugs which block the storage of 5-hydroxytryptamine and related amines. In: Handbuch der experimentellen Pharmakologie. V. Espamer, Ed. Berlin-Heidelberg-New York: Springer 1966.
— M. Lindqvist, K. Fuxe, and B. Hamberger: The effect of (+)-amphetamine on various central and peripheral catecholamine-containing neurones. J. Pharm. Pharmacol. 18, 128–130 (1966a).
— — — and T. Höfkelt: Histochemical and biochemical effects of diethyldithiocarbaminate on tissue catecholamines. J. Pharm. Pharmacol. 18, 60–62 (1966b).
— — and T. Magnussion: 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature (Lond.) 180, 1200 (1957a).
— E. Rosengren, Å. Bertler, and J. Nilsson: Effect of reserpine on the metabolism of catecholamines. In: Psychotropic drugs. Garattini and Ghetti, Ed. Amsterdam: Elsevier Publishing Comp. 1957b.
Chen, G., and C. R. Ensor: Antagonism studies on reserpine and certain CNS depressants. Proc. Soc. exp. Biol. (N. Y.) 87, 602–608 (1954a).
— — and B. Bohner: A facilitation action of reserpine on the central nervous system. Proc. Soc. exp. Biol. (N. Y.) 86, 507–510 (1954b).
Corrodi, H., K. Fuxe, and T. Hökfelt: Refillment of the catecholamine stores with 3,4-dihydroxyphenylalanine after depletion induced by inhibition of tyrosine-hydroxylase. Life Sci. 5, 605–611 (1966).
De Schapdryver, A. F., Y. Piette, and A. L. Delaunois: Brain amines and electroshock threshold. Arch. int. Pharmacodyn. 140, 358–367 (1962).
Ehringer, H., u. O. Hornykiewicz: Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin. Wschr. 38, 1236–1239 (1960).
Fellows, E. J., E. Macko and R. A. McLean: Observations on several cyclohexyl- and phenyl-alkylamines. J. Pharmacol. exper. Ther. 100, 267–272 (1950).
Glowinski, J., S. H. Snyder, and J. Axelrod: Subcellular localization of H3-norepinephrine in the rat brain and the effect of drugs. J. Pharmacol. exp. Ther. 152, 282–292 (1966).
Haas, H.: Über 3-Piperidino-1-phenyl-1-bicycloheptenylpropanol-(1) (Akineton). Arch. int. Pharmacodyn. 128, 204–238 (1960).
—, u. U. Forth: Ëin Beitrag zur Analyse der zentral erregenden Wirkungskomponenten einiger sympathicomimetischer Amine. Arzneimittel-Forsch. 6, 436–445 (1956).
—, u. W. Klavehn: Über 3-Piperidino-1-phenyl-1-bicycloheptenyl-propanol-(1) (Akineton). Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 226, 18–35 (1955).
Hanson, L. C. F.: Evidence that the central action of amphetamine is mediated via catecholamines. Psychopharmacologia (Berl.) 9, 78–80 (1966).
Hess, W. R.: Diencephalon: autonomic and extrapyramidal funktions. Monogr. Biol. Med. 3 (1954).
Holzbauer, M., and M. Vogt: Depression by reserpine of the noradrenaline concentration in the hypothalamus of the cat. J. Neurochem. 1, 8–11 (1956).
Jurna, I.: Reserpine rigidity in the rat—a model for the analysis of anti-parkinson drugs. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 259, 181 (1968a).
-- Inhibition of the effect of reserpine on motor control by drugs depressing rigidity. (In preparation) (1968b).
Kobinger, W.: Reversibility of a facilitatory action of reserpine on the central nervous system by methylamphetamine. Experientia (Basel) 14, 337–338 (1958).
Lands, A. M., and J. I. Grant: The vasopressor action and toxicity of cyclohexyl-ethylamine derivates. J. Pharmacol. exp. Ther. 106, 341–395 (1952).
— V. L. Nash, H. R. Granger, and B. L. Dertinger: The pharmacologic activity of N-methyl-ß-cyclohexyl-isopropylamine hydrochloride. J. Pharmacol. exp. Ther. 89, 382–385 (1947).
Marsh, D. F.: The comparative pharmacology of the cyclohexylamines. J. Pharmacol. exp. Ther. 93, 338–345 (1948).
—, and D. A. Herring: The comparative pressor activity of the optical isomers of cyclohexylisopropylamine and cyclyhexylisopropylmethylamine. J. Pharmacol. exp. Ther. 97, 68–71 (1949).
Moore, K. E., and E. W. Lariviere: Effects of d-amphetamine and restraint on the content of norepinephrine and dopamine in rat brain. Biochem. Pharmacol. 12, 1283–1288 (1963).
Nagatsu, T., M. Levitt, and S. Udenfriend: Conversion of L-tyrosine to 3,4-dihydroxyphenylalanine by cell-free preparations of brain and sympathomimetically innervated tissues. Biochem. biophys. Res. Commun. 14, 543–549 (1964).
P'an, S. Y., W. H. Funderburk, and K. F. Finger: Anticonvulsant effect of nialamide and diphenylhydantoin. Proc. Soc. exp. Biol. (N. Y.) 108, 680–683 (1961).
Picchioni, A. L., L. Chin, and C. Breitner: Relationship between brain levels of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) and susceptibility to electrically induced seizures. Fed. Proc. 21, 416 (1962).
Piette, Y., A. L. Delaunois, A. F. de Schapdryver, and C. Heymans: Imipramine and electroshock threshold. Arch. int. Pharmacodyn. 144, 293–297 (1963).
Pletscher, A., A. Brossi, and K. F. Gey: Benzoquinolizine derivates: a new class of monoamine decreasing drugs with psychotropic action. Int. Rev. Neurobiol. 4, 275–306 (1962).
Quinn, G. P., P. A. Shore, and B. B. Brodie: Biochemical and pharmacological studies of Ro 1-9569 (tetrabenazine), a non-indole tranquilizing agent with reserpine-like effects. J. Pharmacol. exp. Ther. 127, 103–109 (1959).
Radtke, H.: Provokation durch Akineton (personal communication).
Reuse, J.: Modifications par la reserpine de la symptomatologie de crises convulsives provoquees chez le lapin. C. R. Acad. Sci. (Paris) 251, 2248–2249 (1960).
Roos, B.-E., and G. Steg: The effect of L-DOPA and 5-HTP on rigidity and tremor induced by reserpine, chlorpromazine and phenoxybenzamine. Life Sic. 3, 351–360 (1964).
Siegmund, O. H., V. L. Nash, and H. R. Granger: The vasopressor activity of some orally active sympathomimetic amines. J. Pharmacol. exp. Ther. 92, 207–213 (1948).
Steg, G.: Efferent muscle innervation and rigidity. Acta physiol. scand. 61, suppl. 225 (1964).
Udenfriend, S., T. Nagatsu, and P. Zaltzman-Nierenberg: Inhibitions of purifies beef adrenal tyrosine hydroxylase. Biochem. Pharmacol. 14, 837–845 (1965).
Umbach, W.: Klinische Erfahrungen mit Depot-Formen von Antiparkinsonmitteln (Akineton und Kr 339 Knoll). Med. Welt 33, 1634–1637 (1963).
—, u. J. Woywode: Der Effekt eines Stoffes der Amphetamingruppe beim Parkinsonsyndrom mit überwiegender Akinesie. Med. Welt 41, 2329–2336 (1965).
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This work is dedicated to Prof. v. Brücke on the occasion of his 60th birthday.
Supported by a grant of the Deutsche Forschungsgemeinschaft.
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Jurna, I., Regélhy, B. The antagonism between reserpine and some antiparkinson drugs in electroseizure. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 259, 442–459 (1968). https://doi.org/10.1007/BF00538559
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DOI: https://doi.org/10.1007/BF00538559