RTI-7470-44 is a potent, selective and blood-brain barrier (BBB) penetrant human trace amine-associated receptor subtype 1 (hTAAR1) antagonist with an IC50 value of 8.4 nM and a Ki value of 0.3 nM. RTI-7470-44 has moderate metabolic stability, and a favorable preliminary off-target profile. RTI-7470-44 can increase the spontaneous firing rate of mouse ventral tegmental area (VTA) dopaminergic neurons. RTI-7470-44 can be used for researching schizophrenia, drug addiction, and Parkinson's disease (PD)[1].
RTI-7470-44 (10 μM) shows little to no off-target activity with the exception of the benzylpiperazine (BZP) rat brain site and human sigma 2 with inhibition of 75 and 90%, respectively; has a moderate affinity for the BZP rat brain site (Ki=1 μM) and a very weak affinity for human sigma 2 (Ki=8.4 μM)[1].
RTI-7470-44 (40 μM) significantly increases the firing rate of dopaminergic neurons in VTA slices from DAT-IRES-Cre; td-Tomato mice, and reverses the inhibitory effect of RO5166017 (a TAAR1 agonist)[1].RTI-7470-44 (10 μM) has decent stability in human liver microsomes, less stable in mouse liver microsomes and very poor stability in rat liver microsomes[1].Stability of RTI-7470-44 in Human, Rat, and Mouse Liver Microsomes[1]. species half-life (min) clearance, CLINT (mL/min/mg) Human83.914.9Rat9.11274Mouse65.863.5
[1]. Decker AM, et al. Identification of a Potent Human Trace Amine-Associated Receptor 1 Antagonist. ACS Chem Neurosci. 2022 Apr 6;13(7):1082-1095.