Abstract
Bromocriptine, a dopamine agonist, is commonly used in combination with levodopa for the treatment of Parkinson's disease (PD). To investigate the theoretical basis of such combination therapy, we examined the effects of bromocriptine administered alone or in combination with levodopa on dopamine turnover in the striatum of hemi-parkinsonism rats. The parkinsonian striatum showed a 3.4-fold increase of dopamine turnover relative to the control striatum, as often observed in the brain of PD patients. A 7-day course of levodopa therapy markedly increased dopamine turnover in the parkinsonian striatum (53-fold of control level) than in the control striatum (5-fold of the control level). However, bromocriptine specifically and markedly suppressed the levodopa-induced abnormal activation of dopamine turnover in the parkinsonian striatum. Our findings explain the pharmacological basis for the introduction of bromocriptine during long-term levodopa therapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Nutt, J. G., Woodward, W. R., Hammerstad, J. P., and Carter, J. H. 1984. The “on-off” phenomenon in Parkinson's disease. N. Engl. J. Med. 310:483-488.
Woodward, W. R., Olanow, C. W., Becker, R. M., Hasser, R. A., Gauger, L. L., Cedabaum, J. M., and Nutt, J. G. 1993. The effect of levodopa infusion with and without phenylalanine challenges in parkinsonian patients: plasma and ventricular CSF levodopa levels and clinical responses. Neurology 43:1704-1708.
Ogawa, N., Edamatsu, R., Mizukawa, K., Asanuma, M., Kohno, M., and Mori, A. 1993. Degeneration of dopaminergic neurons and free radicals: Possible participation of levodopa. Adv. Neurol. 60:242-250.
Ogawa, N. 1994. Levodopa and dopamine agonists in the treatment of Parkinson's disease: Advantages and disadvantages. Eur. Neurol. 34 (suppl. 3):20-28.
Pardo, B., Mena, M. A., Casarejos, M. J., Paino, C. L., and De Yebens, J. G. 1995. Toxic effects of L-DOPA on mesencephalic cell cultures: protection with antioxidants. Brain Res. 682:133-143.
Walkinshaw, G., and Waters, C. M. 1995. Induction of apoptosis in catecholaminergic PC12 cells by L-DOPA: Implication for the treatment of Parkinson's disease. J. Clin. Invest. 95: 2458-2464.
Imaoka, T., Date, I., Ohmoto, T. and Nagatsu, T. 1998. Significant behavioral recovery in Pakinson's disease model by direct intracerebral gene transfer using continuous infection of a plasmid DNA-liposome complex. Hum. Gene Ther. 9: 1093-1102.
Ogawa, N., Tanaka, K., Asanuma, M., Kawai, M., Masumizu, T., Kohno, M., and Mori, A. 1994. Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl free radicals in vitro. Brain Res. 657:207-213.
Ogawa, N., Haba, K., Asanuma, M., and Mori, A. 1991. Longlasting effects of ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile. Brain Res. 556:271-279.
Rinne, U. K. 1985. Combined bromocriptine-levodopa therapy early in Parkinson's disease. Neurology 35:1196-1198.
Rinne, U. K. 1987. Early combination of bromocriptine and levodopa in the treatment of Parkinso's disease: a 5-year followup. Neurology 37:826-828.
Hely, M. A., Morris, J. G. L., Reid, W. G. J., O'Sullivan, D. J., Williamson, P. M., Rail, D., Broe, G. A., and Margrie, S. 1994. The Sydney multicenter study of Parkinson's disease: a randomised, prospective five year study comparing low dose bromocriptine with low dose levodopa-carbidopa. J. Neurol. Neurosurg. Psychiatry 57:903-910.
Przuntek, H., Welzel, D., Gerlach, M., Blümner, E., Danielczyk, W., Kaiser, H. J., Kraus, P. H., Letzel, H., Riederer, P., and Ñberla, K. 1996. Early institution of bromocriptine in Parkinson's disease inhibits the emergence of levodopa-associated motor side effects. Long-term results of the PRADO study. J. Neural Transm. 103:699-715.
Giménez-Roldán, S., Tolosa, E., Burguera, J., Chacón, J., Liaño, H., and Forcadell, F. 1997. Early combination of bromocriptine and levodopa in Parkinson's disease: A prospective randomized study of two parallel groups overa total followup period of 44 months including an initial 8-month double-blind stage. Clin. Neuropharmacol. 20:67-76.
Bakheit, A. M. O., Henderson, L. M., Moore, A. P., Simpson, J. A., and Thomas, M. 1990. Long-term double masked trial of early treatment with L-Dopa plus bromocriptine versus L-Dopa alone in Parkinson's disease. Eur. Neurol. 30:108-111.
Montastruc, J. L., Rascol, O., and Rascol, A. 1989. A randamised controlled study of bromocriptine versus levodopa in previously untreated parkinsonian patients: a three-year followup. J. Neurol. Neurosurg. Psychiatr. 52:773-775.
Marsden, C. D. 1994. Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 57:672-681.
Calne, D. B. 1993. Treatment of Parkinson's disease. N. Engl. J. Med. 329:1021-1027.
Ogawa, N. 1998. Early introduction of dopamine agonists in the long-term treatment of Parkinson's disease. Neurology 51(suppl. 2):S12-S20.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ogawa, N., Tanaka, Ki. & Asanuma, M. Bromocriptine Markedly Suppresses Levodopa-Induced Abnormal Increase of Dopamine Turnover in the Parkinsonian Striatum. Neurochem Res 25, 755–758 (2000). https://doi.org/10.1023/A:1007530720544
Issue Date:
DOI: https://doi.org/10.1023/A:1007530720544