Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Mar;117(5):781–786. doi: 10.1111/j.1476-5381.1996.tb15260.x

A study of tolerance to apomorphine.

J L Montastruc 1, M E Llau 1, J M Senard 1, M A Tran 1, O Rascol 1, P Montastruc 1
PMCID: PMC1909420  PMID: 8851490

Abstract

1. The present study was designed to investigate tolerance to several pharmacological effects of apomorphine. 2. Changes in blood pressure, heart rate, plasma noradrenaline levels, rectal temperature, respiratory rate and retching plus vomiting were compared after administration of apomorphine (200 micrograms kg-1, i.v. as a bolus) or saline at different time intervals (30, 120 and 720 min) in four groups of chloralose-anaesthetized dogs. 3. The first administration of apomorphine induced a significant decrease in blood pressure and rectal temperature, a marked rise in heart rate with no change in noradrenaline plasma levels or respiratory rate. Emesis occurred in 71% of the animals. 4. A second administration of apomorphine 30 min later failed to modify blood pressure or heart rate. In contrast, the magnitude of apomorphine-induced changes in blood pressure and heart rate was similar to that observed after the first administration when apomorphine was given 120 or 720 min later. 5. The apomorphine-induced decrease in rectal temperature evoked by a second dose of apomorphine was less marked when given 30 and 120 min after the first dose and unchanged when given 720 min later. 6. The number of animals exhibiting retching and vomiting was lower when apomorphine was reinjected after 30 min than when the time between two successive injections of apomorphine was 120 or 720 min. 7. These results show that tolerance to apomorphine involves its cardiovascular, hypothermic and emetic effects. The time course of tolerance to repeated injections of apomorphine is longer for its hypothermic than for its hypotensive or emetic effects. This suggests a tissue-specific regulation of D2 dopamine receptors to repeated injections of apomorphine.

Full text

PDF
781

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen P. H., Gingrich J. A., Bates M. D., Dearry A., Falardeau P., Senogles S. E., Caron M. G. Dopamine receptor subtypes: beyond the D1/D2 classification. Trends Pharmacol Sci. 1990 Jun;11(6):231–236. doi: 10.1016/0165-6147(90)90249-8. [DOI] [PubMed] [Google Scholar]
  2. Caccavelli L., Cussac D., Pellegrini I., Audinot V., Jaquet P., Enjalbert A. D2 dopaminergic receptors: normal and abnormal transduction mechanisms. Horm Res. 1992;38(1-2):78–83. doi: 10.1159/000182494. [DOI] [PubMed] [Google Scholar]
  3. Castro R., Abreu P., Calzadilla C. H., Rodriguez M. Increased or decreased locomotor response in rats following repeated administration of apomorphine depends on dosage interval. Psychopharmacology (Berl) 1985;85(3):333–339. doi: 10.1007/BF00428198. [DOI] [PubMed] [Google Scholar]
  4. Chaudhry A., Granneman J. G. Influence of cell type upon the desensitization of the beta 3-adrenergic receptor. J Pharmacol Exp Ther. 1994 Dec;271(3):1253–1258. [PubMed] [Google Scholar]
  5. Colpaert F. C., Van Bever W. F., Leysen J. E. Apomorphine: chemistry, pharmacology, biochemistry. Int Rev Neurobiol. 1976;19:225–268. doi: 10.1016/s0074-7742(08)60705-9. [DOI] [PubMed] [Google Scholar]
  6. Costentin J., Duterte-Boucher D., Panissaud C., Michael-Titus A. Dopamine D1 and D2 receptors mediate opposite effects of apomorphine on the body temperature of reserpinized mice. Neuropharmacology. 1990 Jan;29(1):31–35. doi: 10.1016/0028-3908(90)90080-b. [DOI] [PubMed] [Google Scholar]
  7. Costentin J., Protais P., Schwartz J. C. Rapid and dissociated changes in sensitivities of different dopamine receptors in mouse brain. Nature. 1975 Oct 2;257(5525):405–407. doi: 10.1038/257405a0. [DOI] [PubMed] [Google Scholar]
  8. Estan L., Senard J. M., Tran M. A., Montastruc J. L., Berlan M. Reserpine induces vascular alpha 2-adrenergic supersensitivity and platelet alpha 2-adrenoceptor up-regulation in dog. Br J Pharmacol. 1990 Oct;101(2):329–336. doi: 10.1111/j.1476-5381.1990.tb12710.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gancher S. T., Nutt J. G., Woodward W. R. Apomorphine infusional therapy in Parkinson's disease: clinical utility and lack of tolerance. Mov Disord. 1995 Jan;10(1):37–43. doi: 10.1002/mds.870100108. [DOI] [PubMed] [Google Scholar]
  10. Gancher S. T., Woodward W. R., Boucher B., Nutt J. G. Peripheral pharmacokinetics of apomorphine in humans. Ann Neurol. 1989 Aug;26(2):232–238. doi: 10.1002/ana.410260209. [DOI] [PubMed] [Google Scholar]
  11. Gancher S., Crabbe J., Garland A., Lea E., Woodward W. Dose- and duration-dependent tolerance to rotational effects of apomorphine in a rat model of Parkinsonism. J Pharmacol Exp Ther. 1995 Jan;272(1):275–281. [PubMed] [Google Scholar]
  12. Grandas F., Gancher S., Lera G., Rodriguez M., Woodward W. R., Nutt J., Obeso J. A. Time interval between repeated injections conditions the duration of motor improvement to apomorphine in Parkinson's disease. Neurology. 1992 Jul;42(7):1287–1290. doi: 10.1212/wnl.42.7.1287. [DOI] [PubMed] [Google Scholar]
  13. Grandas F., Obeso J. A. Motor response following repeated apomorphine administration is reduced in Parkinson's disease. Clin Neuropharmacol. 1989 Feb;12(1):14–22. doi: 10.1097/00002826-198902000-00002. [DOI] [PubMed] [Google Scholar]
  14. Hughes A. J., Lees A. J., Stern G. M. The motor response to sequential apomorphine in parkinsonian fluctuations. J Neurol Neurosurg Psychiatry. 1991 Apr;54(4):358–360. doi: 10.1136/jnnp.54.4.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lahlou S., Petitjean P., Pellissier G., Mouchet P., Feuerstein C., Demenge P. Rostrocaudal localization of cardiovascular responses induced by intrathecal administration of apomorphine in conscious, freely moving rats. J Cardiovasc Pharmacol. 1990 Aug;16(2):331–337. doi: 10.1097/00005344-199008000-00021. [DOI] [PubMed] [Google Scholar]
  16. Lees A. J. Dopamine agonists in Parkinson's disease: a look at apomorphine. Fundam Clin Pharmacol. 1993;7(3-4):121–128. doi: 10.1111/j.1472-8206.1993.tb00226.x. [DOI] [PubMed] [Google Scholar]
  17. Luquin M. R., Laguna J., Herrero M. T., Obeso J. A. Behavioral tolerance to repeated apomorphine administration in parkinsonian monkeys. J Neurol Sci. 1993 Jan;114(1):40–44. doi: 10.1016/0022-510x(93)90046-2. [DOI] [PubMed] [Google Scholar]
  18. Mitchelson F. Pharmacological agents affecting emesis. A review (Part I). Drugs. 1992 Mar;43(3):295–315. doi: 10.2165/00003495-199243030-00002. [DOI] [PubMed] [Google Scholar]
  19. Montastruc J. L., Guiol C., Tran M. A., Lhoste F., Montastruc P. Studies on the cardiovascular actions of apomorphine in dogs: central versus peripheral mechanisms and role of the adrenal medulla. Arch Int Pharmacodyn Ther. 1985 Sep;277(1):92–103. [PubMed] [Google Scholar]
  20. Montastruc J. L., Lapeyre-Mestre M., Llau M. E., Senard J. M., Rascol O., Montastruc P. Naloxone does not prevent apomorphine-induced emesis or hypotension in dogs. Clin Auton Res. 1994 Dec;4(6):303–305. doi: 10.1007/BF01821529. [DOI] [PubMed] [Google Scholar]
  21. Montastruc J. L., Rascol O., Montastruc P. Naloxone or haloperidol but not yohimbine reverse apomorphine-induced respiratory depression. Clin Neuropharmacol. 1992 Oct;15(5):404–407. doi: 10.1097/00002826-199210000-00009. [DOI] [PubMed] [Google Scholar]
  22. Montastruc J. L., Rascol O., Senard J. M. Current status of dopamine agonists in Parkinson's disease management. Drugs. 1993 Sep;46(3):384–393. doi: 10.2165/00003495-199346030-00005. [DOI] [PubMed] [Google Scholar]
  23. Montastruc J. L., Rascol O., Senard J. M., Gualano V., Bagheri H., Houin G., Lees A., Rascol A. Sublingual apomorphine in Parkinson's disease: a clinical and pharmacokinetic study. Clin Neuropharmacol. 1991 Oct;14(5):432–437. doi: 10.1097/00002826-199110000-00007. [DOI] [PubMed] [Google Scholar]
  24. Nicolle E., Pollak P., Serre-Debeauvais F., Richard P., Gervason C. L., Broussolle E., Gavend M. Pharmacokinetics of apomorphine in parkinsonian patients. Fundam Clin Pharmacol. 1993;7(5):245–252. doi: 10.1111/j.1472-8206.1993.tb00238.x. [DOI] [PubMed] [Google Scholar]
  25. Parker S. G., Raval P., Yeulet S., Eden R. J. Tolerance to peripheral, but not central, effects of ropinirole, a selective dopamine D2-like receptor agonist. Eur J Pharmacol. 1994 Nov 14;265(1-2):17–26. doi: 10.1016/0014-2999(94)90218-6. [DOI] [PubMed] [Google Scholar]
  26. Poncet M. F., Damase-Michel C., Valet P., Tran M. A., Montastruc J. L., Montastruc P. Clonidine but not propranolol decreases plasma neuropeptide Y (NPY) levels. Fundam Clin Pharmacol. 1991;5(6):473–480. doi: 10.1111/j.1472-8206.1991.tb00733.x. [DOI] [PubMed] [Google Scholar]
  27. Portillo M., Reverte M., Langin D., Senard J. M., Tran M. A., Berlan M., Montastruc J. L. Effect of a 7-day treatment with idazoxan and its 2-methoxy derivative RX 821002 [correction of RX 821001] on alpha 2-adrenoceptors and non-adrenoceptor idazoxan binding sites in rabbits. Br J Pharmacol. 1991 Sep;104(1):190–194. doi: 10.1111/j.1476-5381.1991.tb12406.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rascol O. J., Montastruc J. L. Cardiovascular effects of apomorphine in humans: evidence for peripheral mechanisms. Clin Neuropharmacol. 1986;9(6):566–569. doi: 10.1097/00002826-198612000-00010. [DOI] [PubMed] [Google Scholar]
  29. Tavernier G., Damase-Michel C., Portolan G., Tran M. A., Montastruc J. L. Is neuropeptide Y co-released with catecholamines in experimental arterial hypertension following sinoaortic denervation? Naunyn Schmiedebergs Arch Pharmacol. 1992 Apr;345(4):431–436. doi: 10.1007/BF00176621. [DOI] [PubMed] [Google Scholar]
  30. Teychenne P. F., Rosin A. J., Plotkin C. N., Calne D. B. Cross tolerance between two dopaminergic ergot derivatives--bromocriptine and lergotrile. Br J Clin Pharmacol. 1980 Jan;9(1):47–50. doi: 10.1111/j.1365-2125.1980.tb04795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Watson J. W., Gonsalves S. F., Fossa A. A., McLean S., Seeger T., Obach S., Andrews P. L. The anti-emetic effects of CP-99,994 in the ferret and the dog: role of the NK1 receptor. Br J Pharmacol. 1995 May;115(1):84–94. doi: 10.1111/j.1476-5381.1995.tb16324.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES