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British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1989 Oct;28(4):435–441. doi: 10.1111/j.1365-2125.1989.tb03524.x

A dose rising study of the safety and effects on serum prolactin of SK&F 101468, a novel dopamine D2-receptor agonist.

G Acton 1, C Broom 1
PMCID: PMC1379994  PMID: 2574051

Abstract

1. SK&F 101468, a non phenolic indolone derivative, has been characterised preclinically as a novel, potent and specific dopamine D2-receptor agonist. 2. Its tolerability and effects on serum prolactin were investigated in 14 healthy male volunteers in a study of the first administration of SK&F 101468 to man. 3. Doses between 80 micrograms and 2.5 mg caused statistically significant (P less than 0.05) lowering of basal and food stimulated serum prolactin, relative to placebo, over a 6 h post treatment period. 4. SK&F 101468 was well tolerated up to 1 mg with symptoms of nausea and postural hypotension at higher doses.

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Selected References

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  1. BIRKMAYER W., HORNYKIEWICZ O. [The L-3,4-dioxyphenylalanine (DOPA)-effect in Parkinson-akinesia]. Wien Klin Wochenschr. 1961 Nov 10;73:787–788. [PubMed] [Google Scholar]
  2. Borison H. L. Area postrema: chemoreceptor trigger zone for vomiting--is that all? Life Sci. 1974 May 16;14(10):1807–1817. doi: 10.1016/0024-3205(74)90399-3. [DOI] [PubMed] [Google Scholar]
  3. Carlson H. E., Wasser H. L., Levin S. R., Wilkins J. N. Prolactin stimulation by meals is related to protein content. J Clin Endocrinol Metab. 1983 Aug;57(2):334–338. doi: 10.1210/jcem-57-2-334. [DOI] [PubMed] [Google Scholar]
  4. Closse A., Frick W., Dravid A., Bolliger G., Hauser D., Sauter A., Tobler H. J. Classification of drugs according to receptor binding profiles. Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(2):95–101. doi: 10.1007/BF00500901. [DOI] [PubMed] [Google Scholar]
  5. Cooper D. S., Ridgway E. C., Kliman B., Kjellberg R. N., Maloof F. Metabolic clearance and production rates of prolactin in man. J Clin Invest. 1979 Dec;64(6):1669–1680. doi: 10.1172/JCI109629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fennell W. H., Taylor A. A., Young J. B., Brandon T. A., Ginos J. Z., Goldberg L. I., Mitchell J. R. Propylbutyldopamine: hemodynamic effects in conscious dogs, normal human volunteers and patients with heart failure. Circulation. 1983 Apr;67(4):829–836. doi: 10.1161/01.cir.67.4.829. [DOI] [PubMed] [Google Scholar]
  7. Franks S., Horrocks P. M., Lynch S. S., Butt W. R., London D. R. Effectiveness of pergolide mesylate in long term treatment of hyperprolactinaemia. Br Med J (Clin Res Ed) 1983 Apr 9;286(6372):1177–1179. doi: 10.1136/bmj.286.6372.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gallagher G., Jr, Lavanchy P. G., Webster C. A., Wilson J. W., Hieble J. P., DeMarinis R. M. 4-[2-(Di-n-propylamino)ethyl]-2(3H)-indolone: a prejunctional dopamine receptor agonist. J Med Chem. 1985 Oct;28(10):1533–1536. doi: 10.1021/jm00148a028. [DOI] [PubMed] [Google Scholar]
  9. Gibson A., Samini M. The effects of bromocriptine on pre-synaptic and post-synaptic alpha-adrenoceptors in the mouse vas deferens. J Pharm Pharmacol. 1979 Dec;31(12):826–830. doi: 10.1111/j.2042-7158.1979.tb13674.x. [DOI] [PubMed] [Google Scholar]
  10. Lemberger L., Crabtree R., Callaghan J. T. Pergolide, a potent long-acting dopamine-receptor agonist. Clin Pharmacol Ther. 1980 May;27(5):642–651. doi: 10.1038/clpt.1980.91. [DOI] [PubMed] [Google Scholar]
  11. Lemberger L., Crabtree R., Clemens J., Dyke R. W., Woodburn R. T. The inhibitory effect of an ergoline derivative (lergotrile, compound 83636) on prolactin secretion in man. J Clin Endocrinol Metab. 1974 Sep;39(3):579–584. doi: 10.1210/jcem-39-3-579. [DOI] [PubMed] [Google Scholar]
  12. McPherson G. A., Beart P. M. The selectivity of some ergot derivatives for alpha 1 and alpha 2-adrenoceptors of rat cerebral cortex. Eur J Pharmacol. 1983 Aug 5;91(4):363–369. doi: 10.1016/0014-2999(83)90159-0. [DOI] [PubMed] [Google Scholar]
  13. Nappi C., Colace G., Di Renzo G. F., Taglialatela M., Amoroso S., Annunziato L., Montemagno U. Domperidone antagonizes bromoergocriptine--induced nausea and vomiting without affecting its inhibition of prolactin secretion in puerperal women. Eur J Clin Pharmacol. 1987;32(5):457–460. doi: 10.1007/BF00637669. [DOI] [PubMed] [Google Scholar]
  14. Olson L., Nyström B., Seiger A. Monoamine fluorescence histochemistry of human post mortem brain. Brain Res. 1973 Dec 7;63:231–247. doi: 10.1016/0006-8993(73)90091-7. [DOI] [PubMed] [Google Scholar]
  15. Parkes D. Bromocriptine. Adv Drug Res. 1977;12:247–344. doi: 10.1016/b978-0-12-013312-3.50008-x. [DOI] [PubMed] [Google Scholar]
  16. Parks L. C., Watanabe A. M., Kopin I. J. Prevention or reversal of levodopa-induced cardiac arrhythmias by decarboxylase inhibitors. Lancet. 1970 Nov 14;2(7681):1014–1015. doi: 10.1016/s0140-6736(70)92818-7. [DOI] [PubMed] [Google Scholar]
  17. Perryman R. L., Rogol A. D., Kaiser D. L., MacLeod R. M., Thorner M. O. Pergolide mesylate: its effects on circulating anterior pituitary hormones in man. J Clin Endocrinol Metab. 1981 Oct;53(4):772–778. doi: 10.1210/jcem-53-4-772. [DOI] [PubMed] [Google Scholar]
  18. Quigley M. E., Ropert J. F., Yen S. S. Acute prolactin release triggered by feeding. J Clin Endocrinol Metab. 1981 May;52(5):1043–1045. doi: 10.1210/jcem-52-5-1043. [DOI] [PubMed] [Google Scholar]
  19. Rowbotham M. C., Joseph M. S., Jones R. T., Keil L. C. Failure of naloxone to reverse apomorphine effects in humans. Psychoneuroendocrinology. 1983;8(1):95–102. doi: 10.1016/0306-4530(83)90045-8. [DOI] [PubMed] [Google Scholar]
  20. Stoof J. C., Kebabian J. W. Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sci. 1984 Dec 3;35(23):2281–2296. doi: 10.1016/0024-3205(84)90519-8. [DOI] [PubMed] [Google Scholar]
  21. Tanner C. M., Goetz C. G., Glantz R. H., Klawans H. L. Pergolide mesylate: four years experience in Parkinson's disease. Adv Neurol. 1987;45:547–549. [PubMed] [Google Scholar]
  22. Thorner M. O., Ryan S. M., Wass J. A., Jones A., Bouloux P., Williams S., Besser G. M. Effect of the dopamine agonist, lergotrile mesylate, on circulating anterior pituitary hormones in man. J Clin Endocrinol Metab. 1978 Aug;47(2):372–378. doi: 10.1210/jcem-47-2-372. [DOI] [PubMed] [Google Scholar]
  23. Van Loon G. R., Sole M. J., Bain J., Ruse J. L. Effects of bromocriptine on plasma catecholamines in normal men. Neuroendocrinology. 1979;28(6):425–434. doi: 10.1159/000122891. [DOI] [PubMed] [Google Scholar]
  24. Weiner R. I., Ganong W. F. Role of brain monoamines and histamine in regulation of anterior pituitary secretion. Physiol Rev. 1978 Oct;58(4):905–976. doi: 10.1152/physrev.1978.58.4.905. [DOI] [PubMed] [Google Scholar]
  25. Willems J. L., Buylaert W. A., Lefebvre R. A., Bogaert M. G. Neuronal dopamine receptors on autonomic ganglia and sympathetic nerves and dopamine receptors in the gastrointestinal system. Pharmacol Rev. 1985 Jun;37(2):165–216. [PubMed] [Google Scholar]

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