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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1976 Jan;56(1):59–68. doi: 10.1111/j.1476-5381.1976.tb06959.x

Stimulant properties of bromocriptine on central dopamine receptors in comparison to apomorphine, (+)-amphetamine and L-DOPA.

A M Johnson, D M Loew, J M Vigouret
PMCID: PMC1666767  PMID: 943193

Abstract

1. The activity of bromocriptine has been investigated in tests for the stimulation of central dopaminergic mechanisms. The results obtained have been compared with those of apomorphine, (+)-amphetamine and L-DOPA. 2. Bromocriptine (2.5 to 10 mg/kg) induced stereotyped sniffing and licking in rats. The stereotypy was more intense than that induced by L-DOPA and less intense than that of apomorphine and (+)-amphetamine over the dose ranges studied. 3. In rats lesioned unilaterally in the substantia nigra by local injection of 6-hydroxydopamine, bromocriptine, like apomorphine and L-DOPA, induced turning contralateral to the side of the lesion. The smallest dose of bromocriptine to induce turning was 0.5 mg/kg. 4. Reserpine-induced catalepsy in mice was antagonized by bromocriptine, with an ED50 of 1.8 mg/kg. It was intermediate in potency to apomorphine and L-DOPA. 5. Spontaneous locomotor activity in mice was stimulated by bromocriptine in a dose-dependent manner from 2.5 to 10 mg/kg after an initial suppression of activity. 6. In all experiments, bromocriptine was characterized by a prolonged duration of activity after a delay in the onset of effect. 7. The stereotyped behaviour induced by bromocriptine was inhibited by prior administration of pimozide, reserpine or alpha-methyl-p-tyrosine. 8. Bromocriptine-induced turning behaviour was abolished by pretreatment with pimozide, and reduced after alpha-methyl-p-tyrosine treatment. 9. The results obtained support the conclusion that bromocriptine acts by stimulating dopamine receptors in the central nervous system and that intact catecholamine synthesis and granular amine storage mechanisms are necessary for it to bring about its effects.

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Selected References

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  1. Andén N. E., Butcher S. G., Corrodi H., Fuxe K., Ungerstedt U. Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur J Pharmacol. 1970;11(3):303–314. doi: 10.1016/0014-2999(70)90006-3. [DOI] [PubMed] [Google Scholar]
  2. Andén N. E., Rubenson A., Fuxe K., Hökfelt T. Evidence for dopamine receptor stimulation by apomorphine. J Pharm Pharmacol. 1967 Sep;19(9):627–629. doi: 10.1111/j.2042-7158.1967.tb09604.x. [DOI] [PubMed] [Google Scholar]
  3. Andén N. E., Strömbom U., Svensson T. H. Dopamine and noradrenaline receptor stimulation: reversal of reserpine-induced suppression of motor activity. Psychopharmacologia. 1973;29(4):289–298. doi: 10.1007/BF00429276. [DOI] [PubMed] [Google Scholar]
  4. CARLSSON A., LINDQVIST M., MAGNUSSON T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature. 1957 Nov 30;180(4596):1200–1200. doi: 10.1038/1801200a0. [DOI] [PubMed] [Google Scholar]
  5. Calne D. B., Teychenne P. F., Claveria L. E., Eastman R., Greenacre J. K., Petrie A. Bromocriptine in Parkinsonism. Br Med J. 1974 Nov 23;4(5942):442–444. doi: 10.1136/bmj.4.5942.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Calne D. B., Teychenne P. F., Leigh P. N., Bamji A. N., Greenacre J. K. Treatment of parkinsonism with bromocriptine. Lancet. 1974 Dec 7;2(7893):1355–1356. doi: 10.1016/s0140-6736(74)92219-3. [DOI] [PubMed] [Google Scholar]
  7. Corrodi H., Fuxe K., Hökfelt T., Lidbrink P., Ungerstedt U. Effect of ergot drugs on central catecholamine neurons: evidence for a stimulation of central dopamine neurons. J Pharm Pharmacol. 1973 May;25(5):409–412. doi: 10.1111/j.2042-7158.1973.tb10037.x. [DOI] [PubMed] [Google Scholar]
  8. Costa E., Groppetti A., Naimzada M. K. Effects of amphetamine on the turnover rate of brain catecholamines and motor activity. Br J Pharmacol. 1972 Apr;44(4):742–751. doi: 10.1111/j.1476-5381.1972.tb07312.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Costall B., Naylor R. J., Olley J. E. Stereotypic and anticataleptic activities of amphetamine after intracerebral injections. Eur J Pharmacol. 1972 Apr;18(1):83–94. doi: 10.1016/0014-2999(72)90135-5. [DOI] [PubMed] [Google Scholar]
  10. Del Pozo E., Del Re R. B., Varga L., Friesen H. The inhibition of prolactin secretion in man by CB-154 (2-Br-alpha-ergocryptine). J Clin Endocrinol Metab. 1972 Nov;35(5):768–771. doi: 10.1210/jcem-35-5-768. [DOI] [PubMed] [Google Scholar]
  11. Dingell J. V., Owens M. L., Norvich M. R., Sulser F. On the role of norepinephrine biosynthesis in the central action of amphetamine. Life Sci. 1967 Jun 1;6(11):1155–1162. doi: 10.1016/0024-3205(67)90197-x. [DOI] [PubMed] [Google Scholar]
  12. Dominic J. A., Moore K. E. Supersensitivity to the central stimulant actions of adrenergic drugs following discontinuation of a chronic diet of alpha-methyltyrosine. Psychopharmacologia. 1969;15(2):96–101. doi: 10.1007/BF00407041. [DOI] [PubMed] [Google Scholar]
  13. Ernst A. M. Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia. 1967;10(4):316–323. doi: 10.1007/BF00403900. [DOI] [PubMed] [Google Scholar]
  14. Ernst A. M., Smelik P. G. Site of action of dopamine and apomorphine on compulsive gnawing behaviour in rats. Experientia. 1966 Dec 15;22(12):837–838. doi: 10.1007/BF01897450. [DOI] [PubMed] [Google Scholar]
  15. Fog R. L., Randrup A., Pakkenberg H. Aminergic mechanisms in corpus striatum and amphetamine-induced stereotyped behaviour. Psychopharmacologia. 1967;11(2):179–193. doi: 10.1007/BF00401255. [DOI] [PubMed] [Google Scholar]
  16. Fuxe K., Ungerstedt U. Histochemical studies on the effect of (positive)-amphetamine, drugs of the imipramine group and tryptamine on central catecholamine and 5-hydroxytryptamine neurons after intraventricular injection of catecholamines and 5-hydroxytryptamine. Eur J Pharmacol. 1968 Sep;4(2):135–144. doi: 10.1016/0014-2999(68)90169-6. [DOI] [PubMed] [Google Scholar]
  17. Hanson L. C. Evidence that the central action of amphetamine is mediated via catecholamines. Psychopharmacologia. 1966;9(1):78–80. doi: 10.1007/BF00427706. [DOI] [PubMed] [Google Scholar]
  18. Johnson A. M., Vigouret J. M., Loew D. M. Proceedings: CB 154 (2-bromo-alpha-ergokryptine, bromocriptin), a potential anti-Parkinson agent. Naunyn Schmiedebergs Arch Pharmacol. 1974;282(Suppl):suppl 282–282:R40. [PubMed] [Google Scholar]
  19. Maj J., Grabowska M., Gajda L. Effect of apomorphine on motility in rats. Eur J Pharmacol. 1972 Feb;17(2):208–214. doi: 10.1016/0014-2999(72)90160-4. [DOI] [PubMed] [Google Scholar]
  20. Morpurgo C., Theobald W. Behavioral reactions to amphetamine in reserpinized rats. Int J Neuropharmacol. 1966 Sep;5(5):375–377. doi: 10.1016/0028-3908(66)90016-5. [DOI] [PubMed] [Google Scholar]
  21. Morpurgo C., Theobald W. Influence of antiparkinson drugs and amphetamine on some pharmacological effects of phenothiazine derivatives used as neuroleptics. Psychopharmacologia. 1964 Sep 11;6(3):178–191. doi: 10.1007/BF00404008. [DOI] [PubMed] [Google Scholar]
  22. Pasteels J. L., Danguy A., Frérotte M., Ectors F. Inhibition de la sécrétion de prolactine par l'ergocornine et la 2-Br-alpha-ergocryptine: action directe sur l'hypophyse en culture. Ann Endocrinol (Paris) 1971 Jan-Feb;32(1):188–192. [PubMed] [Google Scholar]
  23. QUINTON R. M., HALLIWELL G. EFFECTS OF ALPHA-METHYL DOPA AND DOPA ON THE AMPHETAMINE EXCITATORY RESPONSE IN RESERPINIZED RATS. Nature. 1963 Oct 12;200:178–179. doi: 10.1038/200178a0. [DOI] [PubMed] [Google Scholar]
  24. SMITH C. B. ENHANCEMENT BY RESERPINE AND ALPHA-METHYL DOPA OF THE EFFECTS OF D-AMPHETAMINE UPON THE LOCOMOTOR ACTIVITY OF MICE. J Pharmacol Exp Ther. 1963 Dec;142:343–350. [PubMed] [Google Scholar]
  25. SPECTOR S., SJOERDSMA A., UDENFRIEND S. BLOCKADE OF ENDOGENOUS NOREPINEPHRINE SYNTHESIS BY ALPHA-METHYL-TYROSINE, AN INHIBITOR OF TYROSINE HYDROXYLASE. J Pharmacol Exp Ther. 1965 Jan;147:86–95. [PubMed] [Google Scholar]
  26. Stolk J. M., Rech R. H. Enhanced stimulant effects of d-amphetamine in rats treated chronically with reserpine. J Pharmacol Exp Ther. 1968 Sep;163(1):75–83. [PubMed] [Google Scholar]
  27. Svensson T. H., Waldeck B. On the role of brain catecholamines in motor activity: experiments with inhibitors of synthesis and of monoamine oxidase. Psychopharmacologia. 1970;18(4):357–365. doi: 10.1007/BF00402762. [DOI] [PubMed] [Google Scholar]
  28. VAN ROSSUMJ, HURKMANS A. T. MECHANISM OF ACTION OF PSYCHOMOTOR STIMULANT DRUGS. SIGNIFICANCE OF DOPAMINE IN LOCOMOTOR STIMULANT ACTION. Int J Neuropharmacol. 1964 May;3:227–239. doi: 10.1016/0028-3908(64)90012-7. [DOI] [PubMed] [Google Scholar]
  29. Van Rossum J. M. Mode of action of psychomotor stimulant drugs. Int Rev Neurobiol. 1970;12:307–383. doi: 10.1016/s0074-7742(08)60065-3. [DOI] [PubMed] [Google Scholar]
  30. Weissman A., Koe B. K., Tenen S. S. Antiamphetamine effects following inhibition of tyrosine hydroxylase. J Pharmacol Exp Ther. 1966 Mar;151(3):339–352. [PubMed] [Google Scholar]
  31. ZETLER G., MOOG E. Die Bulbocapnin-Katatonie, ihre Synergisten und Antagonisten. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1958;232(2):442–458. [PubMed] [Google Scholar]

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