Biochem/physiol Actions

CTEP is a high-affinity, orally active, potent and selective metabotropic glutamate receptor 5 (mGlu5 or mGluR5) negative allosteric modulator (NAM) and inverse agonist (human/mouse/rat mGlu5 Kd = 1.7/1.8/1.5 nM; IC50 against quisqualate stimulation = 6.4/16.8/8/8 by IP accumulation or 11.4/42/4/6.9 by Ca²⁺ mobilization using human/mouse/rat mGlu5 HEK293 transfectants; IC50 = 40.1 nM against constitutive IP level in human mGlu5 HEK293) with >1000-fold selectivity over 103 molecular targets, including all known mGluRs. CTEP is an excellent tool compound for long-term in vivo studies (in mice and rats) with good pharmacokinetic properties (B/P ratio = 2.6, oral bioavailability ~100%, T1/2 ~18 hrs post 4.5 mg/kg p.o. in mice) and reported to display 30- to 100-fold higher in vivo potency than MPEP and fenobam in two rodent behavioral models sensitive to antianxiety drugs.

CTEP (RO4956371) may be used as a therapeutic to reduce hippocampal long-term depression, protein synthesis, and audiogenic seizures in the fragile X mental retardation 1 (Fmr1) knockout mouse.