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PMID:       11723272
Source:    Neurology  2001 Nov 27;57(10):1829-34

Serotonin 5-HT1A agonist improves motor complications in rodent and primate
parkinsonian models.

Bibbiani F, Oh JD, Chase TN.

Experimental Therapeutics Branch, National Institute of Neurological
Disorders
and Stroke, NIH, Bethesda, MD.

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.

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