Brilaroxazine (RP5063), a Novel Serotonin-Dopamine Stabilizer, Displays Antipsychotic Efficacy in Rodents

Introduction: Brilaroxazine (RP5063) displays high affinity for serotonin (5-HT) 1A/2A/2B/7 and dopamine (D) 2/3/4 moderate D1, transporter (SERT), nicotinic acetylcholine receptor, α4β2. These receptors are associated with multiple psychological disorders. Methods: The pre-clinical assessment involved three standard models emulating human schizophrenia symptoms. apomorphine climbing test (Protais et al., 1976), in 5 groups of 10 NMRI mice, compared brilaroxazine (1, 3, mg/kg i.p.), haloperidol (0.5 vehicle. apomorphine-induced deficit prepulse inhibition (PPI) (Geyer 2001), 15 Wistar rats, (3, 10, 30 (1 mg/kg), dizocilpine effect on locomotion, stereotypy, rearing (Rung al. 2005), 6 olanzapine (6 i.p.) vehicle (and without) induction. Results: decreased across the 1, doses versus controls (p<0.001). This compound dose-dependently reversed PPI effects- at 87 dB (p<0.05) all levels (p<0.01). In dizocilpine-induced model, it controls: (1) spontaneous locomotor activity by 15% (p<0.05, 3 40% (p<0.001, mg/kg) 30% (p<0.01, mg/kg); (2) induced locomotion 25% 49% 47% (3) stereotypy 51% 58% 10- 30-mg/kg, respectively), (only mg/kg, NS). Conclusion: showed animal proof-of-concept mitigating pharmacologically behaviors rodents reflecting psychotic symptoms humans.