RO5166017, or 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.

[4][3] 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.

[7][3] The effects of RO5166017 on monoaminergic neuron firing frequencies were absent in TAAR1 knockout mice and could be reversed by the TAAR1 antagonist RTI-7470-44, indicating that they were mediated by TAAR1 activation.

[8][3][9][10] Likewise, RO5166017 inhibited electrically evoked dopamine release in dorsal striatum (DStr) and nucleus accumbens (NAc) mouse brain slices ex vivo.

[12][13] Neither RO5166017 nor EPPTB had any effect on measures of dopamine reuptake or clearance (tau and half-life) in dopaminergic brain slices ex vivo.

[14][13] Previous in-vitro studies found that TAAR1 could activate several signaling cascades including PKA, PKC, ERK1/2, and CREB.

[1][18][15] As with cocaine, RO5166017 has been found to inhibit nicotine-induced dopamine release in the NAc and to reduce nicotine intake and relapse-like behaviors.