title: Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models.
abstract: 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.
  
  
  CONCLUSIONS
  Pharmaceuticals acting to stimulate 5-HT1A receptors could prove useful in the treatment of the motor response complications in parkinsonian patients.
authors.affiliation: Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1406, USA.
authors.forename: F
authors.initials: F
authors.lastname: Bibbiani
authors.forename: J D
authors.initials: JD
authors.lastname: Oh
authors.forename: T N
authors.initials: TN
authors.lastname: Chase
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D009048:Motor Skills / Q000187:drug effects* / Q000502:physiology; D009930:Organic Chemicals; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D013045:Species Specificity; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000978:Antiparkinson Agents; D009930:Organic Chemicals; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D007980:Levodopa; C443959:sarizotan