SR 27897(Lintitript)

Lintitript (SR 27897) is a highly potent, selective, orally active, competitive and non-peptide cholecystokinin (CCK1) receptor antagonist with an EC50 of 6 nM and a Ki of 0.2 nM. Lintitript displays > 33-fold selectivity more selective for CCK1 than CCK2 receptors (EC50 value of 200 nM). Lintitript increases plasma concentration of leptin and food intake as well as plasma concentration of insulin[1][2][3].

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

Research Areas >> Metabolic Disease

EC50: 6 nM (cholecystokinin (CCK1) receptor)[2]; Ki: 0.2 nM (cholecystokinin (CCK1) receptor)[1]

In vitro, Lintitript (SR 27897) is a competitive antagonist of cholecystokinin (CCK)-stimulated amylase release in isolated rat pancreatic acini (pA2 = 7.50) and of CCK-induced guinea pig gall bladder contractions (pA2 = 9.57)[1]. Lintitript produces concentration dependent inhibition of [125I]CCK binding to CCK1 receptor sites in the rat pancreas (IC50 value of 0.58 nM) and also to CCK 2 sites in the guinea pig cortex (IC2 value of 479 nM). Lintitript inhibits [125I]gastrin binding to gastrin receptors. Lintitript (0.5 nM) increases the dissociation constant of CCK for the CCK A receptor (Kd = 1.8 to 7.2 nM) without modifying the maximum number of receptors (Bmax = 1800 to 1770 fmol/mg)[1].

Lintitript (SR 27897; 1 mg/kg, i.v.) completely reverses the CCK-induced amylase secretion. Lintitript also inhibits CCK-induced gastric and gallbladder emptying in mice (ED50s = 3 and 72 μg/kg, respectively). Lintitript is also very active (ED50 = 27 μg/kg p.o.) in the gall bladder emptying protocol with egg yolk as an inducer of endogenous CCK release[1].

[1]. Gully D, et al. Peripheral biological activity of SR 27897: a new potent non-peptide antagonist of CCKA receptors. Eur J Pharmacol. 1993 Feb 23;232(1):13-9.

[2]. Gouldson P, et al. Contrasting roles of leu(356) in the human CCK(1) receptor for antagonist SR 27897 and agonist SR 146131 binding. Eur J Pharmacol. 1999 Nov 3;383(3):339-46.

[3]. Cano V, et al. Regulation of leptin distribution between plasma and cerebrospinal fluid by cholecystokinin receptors. Br J Pharmacol. 2003 Oct;140(4):647-52.