SR 142948 is an orally bioavailable non-peptide antagonist of neurotensin receptors (NTS; IC50s = 1.19, 0.32, and 3.96 nM for human recombinant NTS receptors expressed in CHO cells, HT-29 cells, and adult rat brain membranes, respectively).1 It inhibits inositol phosphate formation in HT-29 cells (IC50 = 3.9 nM) and intracellular calcium accumulation in CHO cells expressing human NTS receptors. SR 142948 (1 mg/kg, i.v.) inhibits the firing rate of rat ventral pallidum neurons with a longer duration of action than the NTS receptor antagonist SR 48692 .2 It also inhibits neurotensin-induced behavioral responses, including inhibition of neurotensin-induced turning behavior in mice when administered at doses ranging from 40 to 640 mg/kg and hypothermia and analgesia in rats and mice.1
1.Gully, D., Labeeuw, B., Boigegrain, R., et al.Biochemical and pharmacological activities of SR 142948A, a new potent neurotensin receptor antagonistJ. Pharmacol. Exp. Ther.280(2)802-812(1997) 2.Michaud, J.-C., Gueudet, C., and SoubriÉ, P.Effects of neurotensin receptor antagonists on the firing rate of rat ventral pallidum neuronsNeuroreport11(7)1437-1441(2000)