Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models.
BACKGROUND: Serotoninergic transmission in the basal ganglia is known to influence dopaminergic mechanisms and motor function. OBJECTIVE: To evaluate the possibility that serotoninergic 5-HT1A autoreceptors (by regulating the release of serotonin as well as dopamine formed from exogenous levodopa) affect the response alterations complicating levodopa treatment of PD. METHODS: The 5-HT1A receptor agonist sarizotan (EMD128130) was systemically administered alone and together with levodopa to parkinsonian rats and nonhuman primates. RESULTS: In 6-hydroxydopamine-lesioned rats, sarizotan (2.5 mg/kg PO) had no effect on the acute rotational response to levodopa but did attenuate the shortening in motor response duration induced by chronic levodopa treatment. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys, sarizotan (2 mg/kg PO) alone had no effect on parkinsonian severity or on the antiparkinsonian response to levodopa. In contrast, the same dose of sarizotan reduced levodopa-induced choreiform dyskinesias by 91 +/- 5.9%. In both species, the motoric effects of sarizotan were blocked by the selective 5-HT1A antagonist WAY100635 (0.1 mg/kg SC), indicating that the observed sarizotan responses were probably mediated at the 5-HT1A autoreceptor. CONCLUSION: Pharmaceuticals acting to stimulate 5-HT1A receptors could prove useful in the treatment of the motor response complications in parkinsonian patients.[1]References
- Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Bibbiani, F., Oh, J.D., Chase, T.N. Neurology (2001) [Pubmed]
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