Summary
On the basis of the evidence and arguments by Dewhurst that methysergide is a competitive antagonist of a cerebral receptor mediating excitant amine action and elevation of mood we have investigated its predicted value in mania. The effect of this drug interested us further because of its potent and specific antitryptamine action.
Ten in-patients, 8 men and 2 women, with mania who had a history of at least one previous depressive episode and one manic phase were studied. Their ages ranged from 18 to 67 years.
The trial was designed in three phases. First a period of 2 to 6 days on placebo was followed by 8 to 14 days on methysergide (initially by injection), and finally a further period on placebo. The maximum dosage was 6 mg daily for 8 patients but 2 who did not improve were given 9 mg daily.
Eight of the 10 patients showed marked improvement. Two of these did not undergo the third period but of the remaining 6, 5 relapsed on placebo and the remaining patient stayed well. The two failures comprised a patient who had marked paranoid thought disorder and another with a recurrent malignant mania who had failed to respond to high doses of all neuroplegics and ECT in previous and present admissions.
Effects were evident within 24 hours and marked after 48 hours. There was specific remission of all the main manic symptoms, euphoric mood was eliminated and daily activity and sleep normalized. The effect was markedly different from neuroplegic and neuroleptic agents and neither excitomotor nor parkinsonian extrapyramidal side effects were noticed. Some patients complained of aching in legs and thighs, fatigue, or headache. Seven patients showed short periods of transient depression.
The trial showed a specific and potent antimanic action of methysergide. Possible mechanisms whereby methysergide exerts its effects and their relationship to the basic pathophysiology of manias are discussed.
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References
Ashcroft, G. W., T. B. B. Crawford, D. Eccleston, D. F. Sharman, E. J. MacDougall, J. B. Stanton, and J. K. Binns: 5-Hydroxyindole compounds in the cerebrospinal fluid of patients with psychiatric or neurological diseases. Lancet 1966 II, 1049–1052.
Baldratti, G., G. Arcari, and G. K. Suchowsky: Studies on a compound antagonistic to 5-hydroxytryptamine. Experienta (Basel) 21, 396–397 (1965).
Bourne, H. R., W. E. Bunney, Jr., R. W. Colburn, J. M. Davis, J. N. Davis, D. M. Shaw, and A. J. Coppen: Noradrenaline, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in hindbrains of suicidal patients. Lancet 1968 II, 805–808.
Bunag, R. D., and E. Walaszek: The latent vasopressor effect of serotonin in the chicken. Arch. int. Pharmacodyn. 143, 108–118 (1963).
Coppen, A.: The biochemistry of affective disorders. Brit. J. Psychiat. 113, 1237 to 1264 (1967).
Dencker, S. J., U. Malm, B.-E. Roos, and B. Werdinius: Acid monoamine metabolites of cerebrospinal fluid in mental depression and mania. J. Neurochem. 13, 1545–1548 (1966).
Dewhurst, W. G.: On the chemical basis of mood. J. Psychosom. Res. 9, 115–127 (1965).
—: Cerebral amine functions in health and disease. In studies in psychiatry (Eds.; M. Shepherd and D. L. Davies), pp. 289–317. London: Oxford University Press 1968a.
—: New theory of cerebral amine function and its clinical application. Nature (Lond.) 218, 1130–1133 (1968b).
—: Methysergide in mania. Nature (Lond.) 219, 506–507 (1968c).
—, and E. Marley: Methods for quantifying behaviour and cerebral electrical activity and the effect of drugs under controlled conditions. Brit. J. Pharmacol. 25, 671–681 (1965a).
— —: Action of sympathomimetic and allied amines on the central nervous system of the chicken. Brit. J. Pharmacol. 25, 705–727 (1965b).
Doepfner, W.: Biochemical observations on LSD-25 and Deseril. Experientia (Basel) 18, 256–257 (1962).
Fanchamps, A., W. Doepfner, H. Weidmann, u. A. Cerletti: Pharmakologische Charakterisierung von Deseril (R), einem Serotonin-Antagonisten. Schweiz. med. Wschr. 90, 1040–1046 (1960).
Feldman, R. G., and G. H. Glaser: EEG study of methysergide in migraine. Electroenceph. clin. Neurophysiol. 15, 699–702 (1963).
Flückiger, E., and R. Salzmann: Serotoninantagonismus an der Placenta. Experientia (Basel) 17, 131 (1961).
Hájek, J.: Some non-parametric distributions and their applications. (Czech) Čas. pěst. mat. 80, 17–31 (1955).
Kärjä, J., N. T. Kärki, and E. Tala: Inhibition of methysergid of 5-hydroxytryptophan toxicity to mice. Acta pharmacol. (Kbh.) 18, 255–262 (1961).
Koella, W. P.: The mode and locus of action of serotonin in its effects on the recruiting responses and the EEG of cats. In: Molecular basis of some aspects of mental activity (Ed., O. Walaas), Vol. I, pp. 431–442. London: Academic Press 1966.
—, R. Rubin, and U. Schaeppi: Effects of serotonin upon the isolated iris sphincter of the cat. J. Pharmacol. exp. Ther. 155, 440–448 (1967).
Nerebski, J., W. Romanowski, and W. Kadziela: The influence of 1-methyl-d-lysergic butanolamide (Deseril) on EEG changes in rabbits caused by 5-hydroxytryptophane and 5-hydroxytryptamine. Acta physiol. pol. 14, 157–170 (1963).
Oswald, I., G. W. Ashcroft, R. J. Berger, D. Eccleston, J. I. Evans, and V. R. Thacore: Some experiments in the chemistry of normal sleep. Brit. J. Psychiat. 112, 391–399 (1966).
Pokora, J.: Effect of Serpasil, Niamid and Deseril on the excretion of 5-hydroxyindolacetic acid in diurnal urine and on oxidase activity of Ceruloplasmine in human serum. Pol. med. J. 5, 716–722 (1966).
Richter, D.: Tryptophan metabolism in mental illness. In: Amines and schizophrenia (Eds.; H. E. Himwich, S. S. Kety and J. R. Smythies), pp. 167–179. London: Pergamon Press 1967.
Scherbel, A. L., and E. A. Schmid: Effect of serotonin inhibitors on connective tissue disease. Cleveland Clin. Quart. 29, 1–15 (1962).
Tedeschi, D. H., R. E. Tedeschi, and E. J. Fellows: The effects of tryptamine on the central nervous system, including a pharmacological procedure for the evaluation of iproniazid-like drugs. J. Pharmacol. exp. Ther. 126, 223–232 (1959).
Verster, J. P.: Preliminary report on the treatment of mentally disordered patients by intrathecally administered phenothiazine drugs and an antiserotonin substance. S. Afr. med. J. 37, 1086–1089 (1963).
Vojtěchovský, M., E. Kuhn, and E. Horáčková: An attempt to analyse the central effects of Lysenyl and Deseril in clinical conditions (Czech). Activ. nerv. sup. (Praha) 5, 211 (1963).
Votava, Z., I. Podvalová u. M. Vojtěchovský: Unterschiede in der pharmakologischen Wirkung von halluzinogenen und nicht halluzionogenen Lysergsäure-Derivaten (LSD-25, Deseril, Lysenyl, Mesenyl). Arzneimittel-Forsch. 16, 220–222 (1966).
Walsh, J. A.: Antagonism by methysergide of vascular effects of 5-hydroxytryptamine in man. Brit. J. Pharmacol. 30, 518–530 (1967).
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Published in abbreviated form in Nature, 219, 507–508 (1968).
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Haškovec, L., Souček, K. The action of methysergide in manic states. Psychopharmacologia 15, 415–424 (1969). https://doi.org/10.1007/BF00403717
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DOI: https://doi.org/10.1007/BF00403717