The Therapeutic Potential of D1 and D2 Dopamine Agonists in Parkinson’S Disease
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The neurological and biochemical deficits in monkeys with unilateral ventromedial tegmental lesions of the brain stem were compared with those treated with MPTP. The effects of D1 an D2 dopamine agonists on parkinsonian-like symptoms were investigated in both non– human primate models. The stimulation of D2 dopamine receptors elicits a complete relief of tremor in monkeys with unilateral ventromedial tegmental lesions of the brain stem and a relief of parkinsonian-like symptomatology in MPTP-treated monkeys. The combined administration of bromocriptine with L-dopa produces an increased duration of the relief of tremor in monkeys with unilateral ventromedial tegmental lesions of the brain stem when compared with each drug alone. It is postulated that the presence of synaptic dopamine enhances the dopamine agonist activity of bromocriptine at the D2 dopamine receptors. Dopamine agonists which effectively stimulate dopamine autoreceptors and postsynaptic supersensitive, but not normosensitive dopamine receptors, effectively relieve tremor and do not produce severe abnormal involuntary movements in monkeys with unilateral ventromedial tegmental lesions of the brain stem. The therapeutic potential of selective dopamine agonists in treatment of Parkinson’s disease has to be further evaluated.
KeywordsBrain Stem Dopamine Agonist Locus Coeruleus Receptor Reserve MPTP Monkey
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- Goldstein, M., Fuxe, K., Meller, E., Seyfried, C. A., Agnati, L. and Mascagni, F.M. The characterization of the dopaminergic profile of EMD 23,448, an indoly 1–3-butylamine selective actions on presynaptic and supersensitive postsynaptic DA receptor populations. J. Neural Transm. 70:193–215, 1987PubMedCrossRefGoogle Scholar
- Koller, W.C., Fields, J.Z., Gordon, J.H. and Perlow, M.J. Evaluation of ciladopa hydrochloride as a potential anti-parkinson drug. Neuropharmacol. 25:973979, 1986Google Scholar