EPPTB, also known as RO5212773 or RO-5212773, is a drug developed by Hoffmann-La Roche which acts as a potent and selective antagonist or inverse agonist of the trace amine-associated receptor 1 (TAAR1).

[5][2][3] EPPTB has been used in scientific research to demonstrate an important role for TAAR1 in regulation of dopaminergic signaling in the limbic system.

[1][7][2][8][9] Similarly, EPPTB enhances electrically evoked dopamine release in nucleus accumbens (NAcc) but not dorsal striatum (DStr) slices ex vivo.

[1][2][8] As with ex vivo studies, EPPTB enhances VTA dopamine neuron firing rates in vivo in rats and prevents the suppression of the firing of these neurons by high doses of LSD (a serotonergic psychedelic and potent rodent TAAR1 agonist) and by apomorphine (a dopamine D2 receptor agonist).

[12][16][2][9] The TAAR1 partial agonists RO5203648 and RO5263397 enhance the firing rates of dopamine and serotonin neurons in brain slices ex vivo.

[7][13] These findings suggest that the TAAR1 is constitutively and/or tonically active and that TAAR1 partial agonists produce net antagonism.

[20][10] In accordance with the enhanced expected TH activity, higher L-DOPA accumulation was observed in animals treated with T1AM and a DOPA decarboxylase inhibitor.

[10] In accordance with the preceding findings, T1AM also enhanced electrically evoked dopamine release in DStr slices ex vivo.

[10] The preceding findings conflict with previous results that TAAR1 signaling inhibits the firing rates of VTA dopamine neurons.

[10] These differing findings may be related to differential regulation of dopaminergic signaling in the VTA versus the DStr as well as other factors.

[10] On the other hand, previous studies have found that TAAR1 agonism blunted MDMA- and para-chloroamphetamine (PCA)-induced dopamine release in both the ventral and dorsal striatum.

[23] In contrast to RO5166017, injection of EPPTB into the NAcc shell augmented drug-induced reinstatement of cocaine-seeking and enhanced CAMKIIα activity.