RO5166017

RO-5166017 is a drug developed by Hoffmann-La Roche which acts as a potent and selective agonist for the trace amine-associated receptor 1, with no significant activity at other targets. This is important for the study of the TAAR1 receptor, as while numerous other compounds are known which act as TAAR1 agonists, such as methamphetamine, MDMA and 3-iodothyronamine, all previously known TAAR1 agonists are either weak and rapidly metabolized (endogenous ligands), or have strong pharmacological activity at other targets (amphetamines, thyronamines), making it very difficult to assess which effects are due to TAAR1 activation. The discovery of RO-5166017 allows purely TAAR1 mediated effects to be studied, and in animal studies it was shown to prevent stress-induced hyperthermia and block dopamine-dependent hyperlocomotion, as well as blocking the hyperactivity which would normally be induced by an NMDA antagonist. The experiment was done in dopamine transporter knockout mice,[1] and since TAAR1 affects the dopamine transporter, the results could be very different in humans.[2]

RO5166017
Identifiers
IUPAC name
  • (S)-4-[(ethyl-phenyl-amino)-methyl]-4,5-dihydro-oxazol-2-ylamine
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC12H17N3O
Molar mass219.288 g·mol−1
3D model (JSmol)
SMILES
  • NC=2OCC(N=2)CN(CC)c1ccccc1
InChI
  • InChI=1S/C12H17N3O/c1-2-15(11-6-4-3-5-7-11)8-10-9-16-12(13)14-10/h3-7,10H,2,8-9H2,1H3,(H2,13,14)/t10-/m0/s1
  • Key:PPONHQQJLWPUPH-JTQLQIEISA-N

See also

References
  1. Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R, Durkin S, Zbinden KG, Norcross R, Meyer CA, Metzler V, Chaboz S, Ozmen L, Trube G, Pouzet B, Bettler B, Caron MG, Wettstein JG, Hoener MC (2011). "TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity". Proceedings of the National Academy of Sciences USA. 108 (20): 8485–8490. Bibcode:2011PNAS..108.8485R. doi:10.1073/pnas.1103029108. PMC 3101002. PMID 21525407.
  2. Gregory, Miller (16 December 2010). "The Emerging Role of Trace Amine Associated Receptor 1 in the Functional Regulation of Monoamine Transporters and Dopaminergic Activity". Journal of Neurochemistry. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.


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