RTICBM-189

RTICBM-189 is a potent, brain-penetrant allosteric modulator of the cannabinoid type-1 (CB1) receptor with a pIC50 of 7.54 in Ca2+ mobilization assay. RTICBM-189 has pIC50s of 5.29 and 6.25 for hCB1 and mCB1, respectively. RTICBM-189 significantly and selectively attenuates the reinstatement of the cocaine-seeking behavior in rats[1].

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> Cannabinoid Receptor

CB1:7.54 (pIC50)

hCB1:5.29 (pIC50)

mCB1:6.25 (pIC50)

RTICBM-189 (10 mg/kg; i.p.) significantly and selectively attenuates reinstatement of the cocaine-seeking behavior in rats[1]. RTICBM-189 (10 mg/kg; i.p.) rapidly absorbs into systemic circulation, with peak plasma concentration (Cmax,plasma=288.4 ng/mL) observed at tmax,plasma of 0.4 h post-dose. Peak brain levels are also reached at tmax,brain of 0.4 h with a significantly higher Cmax,brain value of 594.6 ng/mL in the brain[1]. Animal Model: Adult male Sprague-Dawley rats weighing 280-300 g[1] Dosage: 10 mg/kg Administration: IP Result: Significantly attenuated drug-induced reinstatement of the cocaine-seeking behavior. Animal Model: Male Sprague-Dawley rats weighing 258-277 g[1] Dosage: 10 mg/kg (Pharmacokinetic Analysis) Administration: IP Result: Plasma: Cmax (288.4 ng/mL), tmax (0.4 hours), CL_F (240.6 mL/min/kg), AUCinf (715.2 ng/mL × h), half-life t1/2 (9.9 hours).Brain: Cmax (594.6 ng/mL), tmax (0.4 hours), CL_F (120.7 mL/min/kg), AUCinf (1438.2 ng/mL × h).

[1]. Nguyen T, et al. Development of 3-(4-Chlorophenyl)-1-(phenethyl)urea Analogues as Allosteric Modulators of the Cannabinoid Type-1 Receptor: RTICBM-189 is Brain Penetrant and Attenuates Reinstatement of Cocaine-Seeking Behavior [published online ahead of print, 2021 Dec 20]. J Med Chem. 2021;10.1021/acs.jmedchem.1c01432.