CP94253

CP94253 is an orally active, brain-penetrant and selective 5-HT_1B receptor agonist with an K_i of 2 nM. CP94253 induces antidepressant-like effects, waking enhancement, sleep inhibition, increased sleep latency, hyperlocomotion, and suppressed aggressive behavior. CP94253 can be used for the research of depression and heightened aggressive behavior^{[1][2][3][4][5][6]}. In Vitro: CP94253 potently and selectively binds to 5-HT_1B receptors (K_i = 2 nM) with minimal affinity for other serotonin receptor subtypes and no significant binding to a broad range of off-target receptors^[3].
CP94253 (1.0-2.0 nM) acts as a competitive inhibitor of [¹²⁵I]iodocyanopindolol binding to rat cerebral cortex membrane 5-HT_1B receptors^[4].
CP94253 (50-100 nM) competitively inhibits [³H]5-HT binding to bovine caudate membrane 5-HT_1D receptors^[4]. In Vivo: CP94253 (1-10 mg/kg; i.p.; single dose) dose-dependently reduces food intake in female Wistar rats with an ED₅₀ of 3.48 mg/kg i.p. for the first hour of access, its hypophagic effect is not mediated by 5-HT_2C receptors, and it has its hypophagic action potentiated by pretreatment with a low, inactive dose of the 5-HT_2C agonist ORG 37684 (HY-103120)^[1].
CP94253 (5 mg/kg; i.p.; single dose) exerts a potent antidepressant-like effect in mice, reducing forced swimming test immobility time by 43%, via stimulation of 5-HT_1B receptors (likely postsynaptic or heteroreceptors), with dopamine and noradrenaline systems contributing to this action^[2].
CP94253 (0.5-10.0 mg/kg; s.c.) activates 5-HT_1B receptors with dose-dependently increasing waking and reducing SWS (at 5.0-10.0 mg/kg) and suppresses REMS across all tested doses in male Wistar rats^[3].
CP94253 (5.0-10.0 mg/kg; s.c.)-induced increases in waking and reductions in SWS can be reversed by pretreatment with 2.0 mg/kg (±) Pindolol (HY-B0982)^[3].
CP94253 (3.2-32 mg/kg; p.o.; daily; 9 days) administered orally to healthy rats induces transient anorexia, sustained reduced body weight gain, and persistent hyperlocomotion at 32 mg/kg, while 3.2 mg/kg and 10 mg/kg doses show no significant effects on these endpoints^[4].
CP94253 (3-17 mg/kg; i.p.; single dose) dose-dependently reduces species-typical aggression in male CFW mice with an ED₅₀ of 7.2 mg/kg for attack bite reduction, an effect specific to 5-HT_1B receptors as shown by antagonism with GR 127935 (HY-123869) and no effect of WAY 100,635 (HY-10349), without concurrent locomotor sedation^[5].
CP94253 (3-10 mg/kg; i.p.; single dose) reduces alcohol-heightened aggression in male CFW mice with a lower ED₅₀ (3.8 mg/kg) than for non-heightened aggression, with dose-dependent effects that only reduce locomotor behaviors at the highest tested dose^[5].
CP94253 (1-10 mg/kg; i.p.; single dose) reduces instigation-heightened aggression in male CFW mice with a lower ED₅₀ (2.7 mg/kg) than for non-instigated aggression, with dose-dependent effects on locomotor behaviors only at higher doses^[5].
CP94253 (5-40 µmol/kg; i.p.; single injection 30 minutes prior to feeding) produces a potent hypophagic effect in mildly deprived rats consuming pellets, with an ID₅₀ of 12.5 µmol/kg, by reducing meal duration and feeding frequency without altering resting behaviour^[6].
CP94253 (5-28 µmol/kg; i.p.; single injection 30 minutes prior to sucrose access) produces a hypophagic effect in mildly deprived rats consuming 10% sucrose, with an ID₅₀ of 22.8 µmol/kg, by reducing meal duration, feeding frequency, and licking burst/cluster frequency without impairing oral motor efficiency^[6].