[3] RO5203648 binds to the mouse, rat, cynomolgus monkey, and human TAAR1 all with high affinity (Ki = 0.5–6.8 nM).

[1][5][2] RO5203648 failed to show these effects in the neurons of TAAR1 knockout mice, indicating that its actions are mediated by interactions with the TAAR1.

[2] RO5203648 alone does not affect electrically evoked dopamine release or reuptake (as measured by tau) in rat nucleus accumbens (NAc) slices ex vivo.

[1][6] RO5203648 did not affect methamphetamine-induced dopamine efflux or reuptake inhibition in rat striatal synaptosomes in vitro.

[7][5][4] Some in-vitro studies have suggested that TAAR1 agonism by amphetamines and β-phenethylamine may mediate induction of monoamine release and reuptake inhibition by these agents.

[7][8][5][4] The dopamine elevations and psychostimulant-like effects of amphetamines are not only preserved but are actually augmented in TAAR1 knockout mice in vivo.

[21] RO5203648 suppressed spontaneous hyperactivity in a novel environment in dopamine transporter (DAT) knockout mice, similarly to antipsychotics like haloperidol and olanzapine.

[21][2] The drug has shown anti-cataleptic, pro-cognitive, antipsychotic-like, antidepressant-like, anxiolytic-like, anti-addictive, and wakefulness-promoting effects in animals.

[2][3][1][6][23] RO5203648, as well as the TAAR1 full agonist RO5256390, have been found to suppress cocaine and methamphetamine self-administration, and hence presumably their rewarding and reinforcing effects.