[1][4][11] RO5263397 can partially and dose-dependently reverse the suppressive effects of RO5256390 on monoaminergic neuron firing in brain slices ex vivo.
[4] RO5263397 has been found to fully prevent methamphetamine-induced dopamine release in rat nucleus accumbens core (NAcc) brain slices ex vivo.
[4] Likewise, it dose-dependently inhibited hyperlocomotion induced by the NMDA receptor antagonists phencyclidine (PCP) and L-687,414 in mice in vivo.
[1][18][14] Similarly, it reduces the expression but not development of conditioned place preference (CPP) by cocaine in mice.
[1][19] In general, the drug has been found to suppress methamphetamine-, cocaine, and nicotine-induced stimulant-like and reinforcing effects in animals in vivo.
[10][1][4][22][16][5][17] The wakefulness-promoting effects of RO5263397 appear to be mediated through dopaminergic signaling, specifically increased activation of dopamine D1 and D2 receptors.
[24][25] The drug has been reported to affect measures of executive function in rats, such as increasing attention, decreasing cognitive flexibility, and modifying impulsivity.
[26] RO5263397 has been reported to inhibit aggression and autism-esque irritability-like behavior induced by serotonin depletion and prenatal exposure to valproic acid.
[7][8] The drug was under development by Roche for treatment of schizophrenia and reached phase 3 clinical trials for this indication by 2019.