RO5166017 explained

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 (TAAR1), with no significant activity at other targets.

The drug 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.

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 receptor antagonist. The experiment was done in dopamine transporter (DAT) knockout mice,^[1] and since TAAR1 affects the DAT, the results could be different in humans.^[2] RO5166017 has also shown robust aversive effects in rodents, similarly to other TAAR1 agonists like RO5256390 and RO5263397.^{[3] [4]}

See also

• EPPTB
• O-Phenyl-3-iodotyramine
• List of aminorex analogues

Notes and 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 . TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity . Proceedings of the National Academy of Sciences USA . 2011 . 108 . 20 . 8485–8490 . 21525407 . 10.1073/pnas.1103029108 . 3101002. 2011PNAS..108.8485R . free .
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. 10.1111/j.1471-4159.2010.07109.x. 3005101. 21073468.
3. Shabani S, Houlton S, Ghimire B, Tonello D, Reed C, Baba H, Aldrich S, Phillips TJ . Robust aversive effects of trace amine-associated receptor 1 activation in mice . Neuropsychopharmacology . 48 . 10 . 1446–1454 . September 2023 . 37055488 . 10425385 . 10.1038/s41386-023-01578-4 .
4. Liu J, Wu R, Johnson B, Zhang Y, Zhu Q, Li JX . Selective TAAR1 agonists induce conditioned taste aversion . Psychopharmacology (Berl) . 239 . 10 . 3345–3353 . October 2022 . 36056214 . 10.1007/s00213-022-06222-5 .