RO-5256390 – (1043495-96-0)

RO5256390 is a trace amine-associated receptor 1 (TAAR1) agonist developed by Hoffmann-La Roche. It exhibits full agonist activity in rats, cynomolgus monkeys, and humans, while acting as a partial agonist in mice. This compound has demonstrated significant potential in preclinical studies for treating various neurological and psychiatric conditions.

In rodent and primate models, RO5256390 displays pro-cognitive and antidepressant-like properties, with brain activation patterns similar to the antipsychotic drug olanzapine. It effectively blocks compulsive overeating behavior in rats and inhibits ATP-induced TNF secretion in mouse bone marrow-derived macrophages. Additionally, RO5256390 has been shown to suppress the firing rates of ventral tegmental area (VTA) dopaminergic neurons and dorsal raphe nucleus (DRN) serotonergic neurons in mouse brain slices ex vivo.

The drug’s effects extend to blocking psychostimulant-induced hyperactivity and producing a brain activation pattern reminiscent of olanzapine, suggesting antipsychotic-like properties. Unlike classical antipsychotics, RO5256390 does not induce extrapyramidal-like symptoms and can reduce haloperidol-induced catalepsy. It also demonstrates robust aversive and locomotor-suppressing effects in rodents, which are dependent on TAAR1 activation.

Furthermore, RO5256390 has been found to decrease motor hyperactivity, novelty-induced locomotor activity, and induce anxiolytic-like effects in a rodent model of attention deficit hyperactivity disorder (ADHD). It has shown pro-cognitive effects in both rodents and monkeys and can strongly suppress rapid eye movement (REM) sleep in rodents. The compound is being investigated for its potential to treat binge eating disorder due to its ability to block compulsive and binge-like eating behavior in rats.

The above information is displayed for information purpose only, and has not been reviewed by EON nor does EON attests or validates the accuracy nor does it constitutes a recommendation or validation.

Sources:

https://en.wikipedia.org/wiki/RO5256390
https://pubchem.ncbi.nlm.nih.gov/compound/24963286
https://www.medchemexpress.com/ro5256390.html
https://www.medkoo.com/products/7538
https://www.sciencedirect.com/science/article/pii/S0014299924005843
https://www.researchgate.net/publication/308925528_The_Trace_Amine-Associated_Receptor_1_Agonist_RO5256390_Blocks_Compulsive_Binge-Like_Eating_in_Rats