Sarizotan

Sarizotan

Sarizotan
Systematic (IUPAC) name
1-[(2R)-3,4-dihydro-2H-chromen-2-yl]-N-([5-(4-fluorophenyl)pyridin-3-yl]methyl)methanamine
Clinical data
Pregnancy cat.
  • N/A
Legal status
  • Discontinued
Routes Oral
Identifiers
CAS number
ATC code None
PubChem
ChemSpider
UNII  YesY
Chemical data
Formula C22H21FN2O 
Mol. mass 348.413 g/mol

Sarizotan (EMD-128,130) is a selective 5-HT1A receptor agonist and D2 receptor antagonist,[1] which has antipsychotic effects,[2][3] and has also shown efficacy in reducing dyskinesias resulting from long-term anti-Parkinsonian treatment with levodopa.[4][5][6][7]

In June 2006, the developer Merck KGaA announced that the development of sarizotan was discontinued, after two sarizotan Phase III studies (PADDY I, PADDY II) failed to meet the primary efficacy endpoint and neither the Phase II findings nor the results from preclinical studies could be confirmed. No statistically significant difference of the primary target variable between sarizotan and placebo could be demonstrated.[8][9]

See also

References

  1. ^ Rabiner, E. A.; Gunn, R. N.; Wilkins, M. R.; Sedman, E.; Grasby, P. M. (2002). "Evaluation of EMD 128 130 occupancy of the 5-HT1A and the D2 receptor: a human PET study with 11CWAY-100635 and 11Craclopride". Journal of psychopharmacology (Oxford, England) 16 (3): 195–199.  
  2. ^ Assié, M.; Ravailhe, V.; Faucillon, V.; Newman-Tancredi, A. (2005). "Contrasting contribution of 5-hydroxytryptamine 1A receptor activation to neurochemical profile of novel antipsychotics: frontocortical dopamine and hippocampal serotonin release in rat brain". The Journal of Pharmacology and Experimental Therapeutics 315 (1): 265–272.  
  3. ^ Auclair, A.; Galinier, A.; Besnard, J.; Newman-Tancredi, A.; Depoortère, R. (2007). "Putative antipsychotics with pronounced agonism at serotonin 5-HT1A and partial agonist activity at dopamine D2 receptors disrupt basal PPI of the startle reflex in rats". Psychopharmacology 193 (1): 45–54.  
  4. ^ Bibbiani, F.; Oh, J. D.; Chase, T. N. (2001). "Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models". Neurology 57 (10): 1829–1834.  
  5. ^ Bartoszyk, G.; Van Amsterdam, C.; Greiner, H.; Rautenberg, W.; Russ, H.; Seyfried, C. (2004). "Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile". Journal of neural transmission (Vienna, Austria : 1996) 111 (2): 113–126.  
  6. ^ Bara-Jimenez, W.; Bibbiani, F.; Morris, M.; Dimitrova, T.; Sherzai, A.; Mouradian, M.; Chase, T. (2005). "Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease". Movement disorders : official journal of the Movement Disorder Society 20 (8): 932–936.  
  7. ^ Grégoire, L.; Samadi, P.; Graham, J.; Bédard, P.; Bartoszyk, G.; Di Paolo, T. (2009). "Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys". Parkinsonism & related disorders 15 (6): 445–452.  
  8. ^ "Merck KGaA: Development of Sarizotan to treat Parkinson's patients will not be pursued". Ad Hoc News. 23 June 2006. 
  9. ^ "Merck KGaA discontinues development of Parkinson drug Sarizotan UPDATE". Forbes. 23 June 2006.