Sarizotan Explained

Sarizotan (EMD-128,130) is a selective 5-HT_1A 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

• Osemozotan
• Piclozotan
• Robalzotan

Notes and References

1. Rabiner EA, Gunn RN, Wilkins MR, Sedman E, Grasby PM . Evaluation of EMD 128 130 occupancy of the 5-HT1A and the D2 receptor: a human PET study with [11C]WAY-100635 and [11C]raclopride . Journal of Psychopharmacology . 16 . 3 . 195–9 . September 2002 . 12236624 . 10.1177/026988110201600301 . 12943982 .
2. Assié MB, Ravailhe V, Faucillon V, Newman-Tancredi A . 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 . 265–72 . October 2005 . 15987834 . 10.1124/jpet.105.087163 . 9262233 .
3. Auclair AL, Galinier A, Besnard J, Newman-Tancredi A, Depoortère R . 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 . July 2007 . 17393144 . 10.1007/s00213-007-0762-7 . 23379049 .
4. Bibbiani F, Oh JD, Chase TN . Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models . Neurology . 57 . 10 . 1829–34 . November 2001 . 11723272 . 10.1212/wnl.57.10.1829 . 24836560 .
5. Bartoszyk GD, Van Amsterdam C, Greiner HE, Rautenberg W, Russ H, Seyfried CA . Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile . Journal of Neural Transmission . 111 . 2 . 113–26 . February 2004 . 14767715 . 10.1007/s00702-003-0094-7 . 25419329 .
6. Bara-Jimenez W, Bibbiani F, Morris MJ, Dimitrova T, Sherzai A, Mouradian MM, Chase TN . Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease . Movement Disorders . 20 . 8 . 932–6 . August 2005 . 15791634 . 10.1002/mds.20370 . 46098045 .
7. Grégoire L, Samadi P, Graham J, Bédard PJ, Bartoszyk GD, Di Paolo T . Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of L-Dopa in parkinsonian monkeys . Parkinsonism & Related Disorders . 15 . 6 . 445–52 . July 2009 . 19196540 . 10.1016/j.parkreldis.2008.11.001 .
8. News: Merck KGaA: Development of Sarizotan to treat Parkinson's patients will not be pursued. 23 June 2006. Ad Hoc News.
9. News: Merck KGaA discontinues development of Parkinson drug Sarizotan UPDATE. 23 June 2006. Forbes.