Chronic treatment with L-DOPA, but not bromocriptine induces dyskinesia in MPTP-parkinsonian monkeys. Correlation with [3H]spiperone binding.
A group of 5 monkeys developed a severe parkinsonian syndrome after intravenous administration of the toxin MPTP. One remained untreated while two animals were treated daily for 5 months with supramaximal doses of Sinemet and two with bromocriptine orally. Both drugs relieved the parkinsonian symptoms but the animals on Sinemet developed after 2 weeks prominent lingual dyskinesia which remained visible after each dose until the end of the experiment. In the two animals on bromocriptine no dyskinesia was observed. After sacrifice, the levels of dopamine and [3H]spiperone binding were studied bilaterally in the anterior and posterior caudate nucleus, anterior and posterior putamen and in the nucleus accumbens. The loss of dopamine was equivalent in the Sinemet and the bromocriptine treated animals (more than 90%) and there was a complete disappearance of the substantia nigra pars compacta. In all structures studied, the Bmax for [3H]spiperone binding was on average 10% higher in the Sinemet than in the bromocriptine-treated animals. We therefore believe that L-DOPA and bromocriptine affect denervated postsynaptic dopamine receptors differently, that bromocriptine is less likely to induce agonist supersensitivity and that this probably explains the lesser tendency to induce dyskinesia after chronic treatment.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001971:Bromocriptine / Q000009:adverse effects* / Q000627:therapeutic use; D002090:Butyrophenones / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D008252:Macaca fascicularis; D009069:Movement Disorders / Q000209:etiology*; D010302:Parkinson Disease, Secondary / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D011725:Pyridines; D013134:Spiperone / Q000378:metabolism*; D013997:Time Factors
D002090:Butyrophenones; D011725:Pyridines; D001971:Bromocriptine; D007980:Levodopa; D013134:Spiperone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine