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Effects of serotonin 5‐HT1A agonist in advanced Parkinson's disease
Author(s) -
BaraJimenez William,
Bibbiani Francesco,
Morris Michael J.,
Dimitrova Tzvetelina,
Sherzai Abdullah,
Mouradian Maral M.,
Chase Thomas N.
Publication year - 2005
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.20370
Subject(s) - levodopa , dopaminergic , serotonergic , parkinson's disease , dopamine , agonist , autoreceptor , pramipexole , serotonin , 5 ht1a receptor , psychology , dopamine agonist , medicine , endocrinology , neuroscience , pharmacology , 5 ht receptor , receptor , disease
Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5‐HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5‐HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3‐week, double‐blind, placebo‐controlled, proof‐of‐concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa‐induced dyskinesias and prolonged its antiparkinsonian response ( P ≤ 0.05). Under the conditions of this study, our findings suggest that 5‐HT1A receptor stimulation in levodopa‐treated parkinsonian patients can modulate striatal dopaminergic function and that 5‐HT1A agonists may be useful as levodopa adjuvants in the treatment of PD. © 2005 Movement Disorder Society