Summary
The endocrinological actions of quipazine, a direct serotonin receptor agonist, were investigated in both normal subjects (NS) and individuals with neurological disorders,i.e., Huntington's disease (HD), myoclonic epilepsy (ME) and cluster headache (CH). In both normal subjects and neurologic patients inconsistent and variable changes in the secretion of anterior pituitary hormones were observed. In fact, oral administration of 50 mg of quipazine elicited a rise in plasma GH in only 9/23 subjects investigated (3 NS, 2 HD, 1 ME, 3 CH), decreased GH in 4 subjects (1 NS, 2 HD, 1 CH) and left unmodified plasma GH in the remaining 10 subjects. Only 7/23 subjects showed a positive PRL response to quipazine (2 NS, 1 HD, 1 ME, 3 CH), in one subject (CH) PRL was inhibited while the drug was ineffective in the remaining 15 subjects. For gonadotropins, 5/21 subjects (2 NS, 1 HD, 2 CH) had a positive LH response and 3/20 subjects (1 NS, 1 ME, 1 CH) had a positive FSH response. In one subject (HD) there was inhibition of baseline LH levels and no effects were present in the remaining individuals. No changes in basal TSH levels were present in the 6 subjects investigated (4 NS, 2 ME). Quipazine was instead competent to increase plasma cortisol levels in 6/8 normal subjects. Pharmacodynamic, mainly gastrointestinal, effects of the drug were present in about 50% of the subjects but were not or only poorly correlated with the endocrine responses. Collectively, based on the neuropharmacologic profile of the drug, and in contrast to many animal data, these findings do not support a major role for the serotoninergic system on basal anterior pituitary hormone secretion in man, possibly with the exception of the ACTH-cortisol secretion.
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References
Anthony, M., Lance, J. W., Lord, G.: Migrainous-neuralgia. Blood histamine levels and clinical response to H1 and H2 receptor blockade. In: Current Concepts in Migraine Research (Greene, R., ed.), pp. 149–151. Academic Press. 1978.
Baum, C. K., Tudor, R., Landon, J. A simple competitive protein binding assay for plasma cortisol. Clinica Chim. Acta55, 147–154 (1974).
Beck-Peccoz, P., Ferrari, C., Rondena, M., Paracchi, A., Faglia, G. Failure of oral 5-hydroxytryptophan administration to affect prolactin secretion in man. Hormone Res.7, 303–307 (1976).
Benkert, O., Laakman, G., Souvatzoglou, A., von Werder, K. Missing indicator function of growth hormone and luteinizing hormone blood levels for dopamine and serotonin concentrations in the human. J. Neural Transm.34, 291–299 (1973).
Berger, P. A., Barchas, J. D., Vernikos-Danellis, J. Serotonin and pituitaryadrenal function. Nature (Lond.)248, 242–246 (1974).
Brambilla, F., Smeraldi, E., Sacchetti, E., Negri, F., Cocchi, D., Müller, E. E. Deranged anterior pituitary responsiveness to hypothalamic hormones in depressed patients. Arch. Gen. Psychiat.35, 1231–1238 (1978).
Brodie, H. K. H., Sack, R., Siever, L. Serotonin and Behavior (Barcbas, J., Usdin, E., eds.), pp. 549–562. New York: Academic Press. 1973.
Bruyn, G. W.: The biochemical basis of migraine: a critique. In: Clinical Neuropharmacology, Vol. 1 (Klawans, H. L., ed.), pp. 185–213. 1976.
Caraceni, T., Panerai, A. E., Parati, E. A., Cocchi, D., M:üler, E. E. Altered growth hormone and prolactin responses to dopaminergic stimulation in Huntington's chorea. J. Clin. Endocrinol. Metab.44, 870–875 (1977).
Cavagnini, F., Panerai, A. E., Valentini, F., Bulgheroni, P., Peracchi, M., Pinto, M. Inhibition of ACTH response to oral and intravenous metyrapone by antiserotoninergic treatment in man. J. Clin. Endocrinol. Metab.41, 143–148 (1975).
Chadwich, O., Reynolds, E. H., Marsden, C. D. Relief of action myoclonus by 5-hydroxytryptophan. Lancet2, 111–112 (1974).
Chen, H. J., Meites, J. Effects of biogenic amines and TRH on release of prolactin and TSH in the rat. Endocrinology96, 10–14 (1975).
Daughaday, W. H. The Adenohypophysis. In: Textbook of Endocrinology (Williams, R. H., ed.), pp. 31–79. Philadelphia: W. B. Saunders Co. 1974.
del Pozo, E., Lancranjan, I. Clinical use of drugs modifying the release of anterior pituitary hormones. In: Frontiers in Neuroendocrinology, Vol. 5 (Ganong, W., Martini, L., eds.), pp. 207–247. New York: Raven Press. 1978.
Enna, S. J., Stern, L. Z., Wastek, J., Yamamura, H. I. Neurobiology and pharmacology of Huntington's disease. Life Sci.20, 205–212 (1977).
Frantz, A., Kleinberg, D., Noel, G. Studies on prolactin in man. Recent Prog. Horm. Res.28, 527–590 (1972).
Fuller, R. W. Drugs influencing serotoninergic neurotransmission. In: Neuroactive Drugs in Endocrinology: Physiologic, Diagnostic and Therapeutic Applications (Müller, E. E., ed.), pp. 123–135. Amsterdam: Elsevier/North-Holland. 1980.
Fuxe, K., Jonsson, G. Serotonin. New Vistas (Costa, E., Gessa, G. L., Sandler, M., eds.), pp. 1–12. New York: Raven Press. 1974.
Gallo, R. V., Möberg, G. P. Serotonin mediated inhibition of episodic luteinizing hormone release during electrical stimulation of the arcuate nucleus in ovariectomized rats. Endocrinology100, 945–954 (1977).
Grabowska, M., Kiewicz, A., Michaluk, J. A possible interaction of quipazine with central dopamine structures. J. Pharm. Pharmacol.26, 74–76 (1974).
Hamon, M., Bourgoin, S., Enjalbert, A., Bockaert, J., Hery, F., Ternaux, J. P., Glowinski, J. The effects of quipazine on 5-HT metabolism in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol.294, 99–108 (1976).
Handwerger, S., Plonk, J. W., Lebovitz, H. E., Bivens, C. H., Feldman, J. M. Failure of 5-hydroxytryptophan to stimulate prolactin and growth hormone secretion in man. Hormone Metab. Res.7, 214–217 (1975).
Hong, E., Sancilio, F. L., Vargas, R., Pardo, E. G. Similarities between the pharmacological actions of quipazine and serotonin. Europ. J. Pharmacol.6, 274–280 (1969).
Imura, H., Nakai, Y., Yoshimi, T. Effect of 5-hydroxytryptophan on growth hormone and ACTH release in man. J. Clin. Endocrinol. Metab.36, 204–206 (1973).
Jordan, D., Poncet, C., Mornex, R., Ponsin, G. Participation of serotonin in thyrotropin release. I. Evidence for the action of serotonin on thyrotropin releasing hormone release. Endocrinology103, 414–419 (1978).
Kamberi, I. A., Mical, R. S., Porter, J. C. Effect of anterior pituitary perfusion and intraventricular injection of catecholamines and indoleamines on LH release. Endocrinology87, 1–12 (1970).
Kamberi, I. A., Mical, R. S., Porter, J. C. Effect of melatonin and serotonin on the release of FSH and prolactin. Endocrinology88, 1288–1293 (1971).
Kordon, C., Blake, C. A., Terkel, J., Sawyer, C. H. Participation of the 5-HT-containing neurons in the suckling-induced rise in plasma prolactin levels in lactating rats. Neuroendocrinology13, 213–233 (1973/74).
Krieger, H. P., Krieger, D. T. Chemical stimulation of the brain: effect on adrenal corticoid release. Am. J. Physiol.218, 1632–1641 (1970).
Lancrajan, I., delPozo, E., Picciolini, E., D'Antona, N., Genazzani, A. Effect of two serotonin antagonists on prolactin release induced by breast stimulation in post-partum women. Hormone Res.10, 14–19 (1979).
Locatelli, V., Cocchi, D., Panerai, A. E., Gil-Ad, I., Mantegazza, P., Secchi, C., Müller, E. E. Drug-induced changes of brain serotoninergic tone and insulin-induced growth hormone release in the dog. Neuroendocrinology25, 84–104 (1978).
Malick, J. B., Doren, E., Barnett, A. Quipazine-induced head-twitch in mice. Pharmac. Biochem. Behav.6, 325–329 (1977).
Marchlewska-Koj, A., Krulich, L. The role of central monoamines in the stress-induced prolactin release in the rat. Fed. Proc. Fed. Am. Soc. Exp. Biol.34, 252 (1975).
McCann, S., Krulich, L., Ojeda, S. R., Negro-Vilar, A., Vijayan, E. Neurotransmitters in the control of anterior pituitary function. In: Central Regulation of the Endocrine Systems (Fuxe, K., Hökfelt, T., Luft, R., eds.), pp. 329–347. New York-London: Plenum Press. 1979.
McIndoe, J. H., Turkington, R. W. Stimulation of human prolactin secretion by intravenous infusion of 1-tryptophan. J. Clin. Invest.52, 1972–1978 (1973).
McLeod, R. M., Login, I. S. Regulation of prolactin secretion through dopamine, serotonin and the cerebrospinal fluid. In: Nonstriatal Dopaminergic Neurons (Costa, E., Gessa, G. L., eds.), pp. 147–157. New York: Raven Press. 1977.
Meltzer, H. Y., Fang, V. S., Paul, S. M., Kaluskar, R. Effect of quipazine on rat plasma prolactin levels. Life Sci.19, 1075–1078 (1976).
Mess, B., Peter, L. Effect of intracerebral serotonin administration on pituitary thyroid function. Endocrinol. Exp.9, 105–113 (1975).
Midgley, A. G., jr. Radioimmunoassay method for human chorionic gonadotropin and human LH. Endocrinology79, 10–18 (1966).
Midgley, A. G., jr. Radioimmunoassay for human follicle-stimulating hormone. J. Clin. Endocrinol. Metab.27, 295–299 (1967).
Müller, E. E., Nisticò, G., Scapagnini, U. Neurotransmitters and Anterior Pituitary Function. New York: Academic Press. 1978.
Müller, E. E., Brambilla, F., Cavagnini, F., Peracchi, M., Panerai, A. E. Slight effect of 1-tryptophan on GH release in normal human subjects. J. Clin. Endocr. Metab.39, 1–6 (1974).
Müller, E. E., Udeschini, G., Secchi, C., Zambotti, F., Panerai, A. E., Vicentini, L., Cocola, F., Mantegazza, P. Inhibitory role of the serotoninergic system on hypoglycaemia-induced growth hormone release in the dog. Acta Endocrinol. (Kbh.)82, 71–91 (1976).
Müller, E. E., Parati, E. A., Panerai, A. E., Cocchi, D., Caraceni, T. Growth hormone hyperresponsiveness to dopaminergic stimulation in Huntington's chorea. Neuroendocrinology28, 313–319 (1979).
Mulloy, A. L., Möberg, G. B. Effects of p-chlorophenylalanine and raphe lesions on diurnal prolactin release in the rat. Fed. Proc. Fed. Am. Soc. Exp. Biol.34, 251 (1975).
Neill, J. D. Effect of “stress” on serum prolactin and luteinizing hormone levels during the estrous cycle of the rat. Endocrinology87, 1192–1197 (1970).
Odell, W. D., Wilberg, J. F., Utiger, R. D. Studies of thyrotropin physiology by means of radioimmunoassay. Recent Prog. Horm. Res.23, 47–85 (1967).
Plonk, J. W., Bivens, C. H., Feldman, J. M. Inhibition of hypoglycemiainduced cortisol secretion by the serotonin antagonist cyproheptadne. J. Clin. Endocrinol. Metab.38, 836–840 (1974).
Plonk, J., Feldman, J. M. Modification of adrenal function by the antiserotonin agent cyproheptadine. J. Clin. Endocrinol. Metab.42, 291–295 (1976).
Rodriguez, R., Rojas-Ramirez, A., Drucker-Colin, R. R. Serotonin like actions of quipazine on the central nervous system. Europ. J. Pharmacol.24, 164–171 (1973).
Ruch, W., Mixter, R. C., Russell, R. M., Garcia, G. F., Gale, C. C. Aminergic and thermoregulatory mechanisms in hypothalamic regulation of growth hormone in cats. Am. J. Physiol.233, E61-E69 (1977).
Schalch, S., Parker, M. A sensitive double-antibody immunoassay for human growth hormone in plasma. Nature203, 1141–1142 (1964).
Schalch, S., Reichlin, S. Stress and growth hormone release. In: Growth Hormone (Pecile, A., Müller, E. E., eds.), pp. 211–225. Amsterdam: Excerpta Medica. 1968.
Smythe, G. A., Compton, P. S., Lazarus, L. Serotoninergic control of human growth hormone secretion: the action of 1-dopa and 2-bromo-α-ergocryptine. In: Growth Hormone and Related Peptides (Pecile, A., Müller, E. E., eds.), pp. 222–235. Amsterdam: Excerpta Medica. 1976.
Toivola, P. T. K., Gale, C. C. Stimulation of growth hormone release by microinjection of norepinephrine into hypothalamus of baboons. Endocrinology90, 895–902 (1972).
Tuomisto, J., Ranta, T., Mannisto, P., Saarinen, A., Leppaluoto, J. Neurotransmitter control of thyrotropin secretion in the rat. Europ. J. Pharmacol.30, 221–229 (1975).
Van Loon, G. R. Brain catecholamines and ACTH secretion. In: Frontiers in Neuroendocrinology, Vol. 3 (Ganong, W. F., Martini, L., eds.), pp. 209–248. New York: Oxford University Press. 1973.
Van Woert, M. H., Rosenbaum, D., Howieson, J., Bowers, M. B., jr. Longterm therapy of myoclonus and other neurologic disorders with L-5-hydroxytryptophan and carbidopa. N. Engl. J. Med.296, 70–74 (1977).
Vermes, J., Molnar, D., Teledgy, G. The effect of hypothalamic serotonin on compensatory adrenal function. Acta Physiol. Acad. Sci. Hung.43, 27–32 (1973).
Vjayan, E., Krulich, L., McCann, S. M. Stimulation of growth hormone release by intraventricular administration of 5-HT or quipazine in unanesthetized male rats. Proc. Soc. Exp. Biol. Med.159, 210–211 (1978).
Wiebe, R. H., Handwerger, S., Hammond, C. B. Failure of L-tryptophan to stimulate prolactin secretion in man. J. Clin. Endocrinol. Metab.45, 1310–1312 (1977).
Woolf, P. D., Lee, L. Effect of the serotonin precursor, tryptophan, on pituitary hormone secretion. J. Clin. Endocrinol. Metab.45, 123–133 (1977).
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Parati, E.A., Zanardi, P., Cocchi, D. et al. Neuroendocrine effects of quipazine in man in health state or with neurological disorders. J. Neural Transmission 47, 273–297 (1980). https://doi.org/10.1007/BF01247322
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DOI: https://doi.org/10.1007/BF01247322