Disease relevance of Lintitript

• Administration of PD140548 (10 mg/kg, i.v.) and SR 27897B (0.6 mg/kg, i.v.) significantly inhibited the pressor effects of CCK (35 and 47%, respectively), whilst reversing the bradycardic responses to a tachycardia [1].
• In this study in patients with advanced pancreatic cancer, we evaluated the use of fluorodeoxyglucose (FDG) PET compared with magnetic resonance imaging (MRI) in monitoring hormonal therapy using a highly selective, non-peptide CCK receptor antagonist (SR 27897B) [2].

High impact information on Lintitript

• RSA phases were also re-established when the "alimentary" type of cholecystokinin receptors (CCKA) were blocked by selective antagonists such as L364,718 or SR27897 (1 mg/kg i.v.). The latter had better brain accessibility than L364,718 [3].
• Under our conditions, SR-27897 increased plasma concentration of leptin both in fed and food-deprived rats [4].
• Moreover, the competition data for SR27897, 2-NAP and YM220 were consistent with the interaction of these compounds at two binding sites [5].
• 4. In competition studies, the low affinity of the CCKA receptor antagonists, L-364,718; SR27897 and 2-NAP, suggest that, under the assay conditions employed, [3H]-JB93182 (0.3 nM) does not label CCKA receptors in the rat cortex [6].
• The aim of the present study was to investigate the effects of cholecystokinin (CCK) CCK(A) and CCKB receptor antagonists SR 27897 B, devazepide, L 365260 and PD 135158 (CAM 1028) on exploratory behaviour in the elevated zero-maze in the rat [7].

Biological context of Lintitript

• Lintitript distinctly accelerated gastric emptying of solids, while gastric emptying of liquids was not significantly altered [8].
• Effects of the CCK(A) receptor antagonists SR 27897B and PD140548 on baroreflex function in conscious rats [1].
• In most tests the i.p./p.o. ratio for SR 27897 was near unity, suggesting a high oral bioavailability of the compound [9].
• SR 27897 was also very active (ED50 = 27 micrograms/kg p.o.) in the gall bladder emptying protocol with egg yolk as an inducer of endogenous CCK release [10].

Anatomical context of Lintitript

• With increased interest in the pharmacology of cholecystokininA (CCKA) receptors, including their trophic and mitogenic effects, the actions of two new non-peptide CCKA receptor antagonists, PD140548 and SR 27897B, were investigated in a convenient model system, the rat isolated nodose ganglion [11].
• Taken together, these findings support the notion that SR 27897 behaves as a potent CCK-A antagonist able to cross the blood brain barrier [9].

Associations of Lintitript with other chemical compounds

• The excitatory response increased after administration of the cholecystokinin A (CCK(A)) receptor antagonists lorglumide (3x10(-6) M: +44.1%), devazepide (10(-8) M: +19.4%; 10(-7) M: +30.0%) and SR-27897 (10(-10) M: +21.8%, 10(-8) M: +47.0%, P<0.05, n=8) [12].
• These binding sites were of the CCKA type, as demonstrated by the differential inhibition of the binding of [125I]CCK-8-S and CCK-8-S-induced 45Ca2+ efflux by the specific CCKA antagonist SR 27897 and the specific CCKB antagonist PD 134,308 [13].
• Competition studies were also conducted using a number of previously well-characterized CCK-receptor selective ligands; JB93182, YF476, PD-134,308, SR27897, dexloxiglumide, L-365,260 and L-364,718 [14].
• The potentiation of the NMDA response induced by these sigma ligands was abolished by the selective CCKA receptor antagonist SR 27897, but not by the CCKB antagonist Cl-988 [15].
• The potency of the contraction induced by CCK-8, desulphated CCK-8, and gastrin-I, and the effect of the CCK-A (loxiglumide and SR 27897) and the CCK-B (YM022 and L-365 260) specific receptor antagonists were compared [16].

Gene context of Lintitript

• Lintitript markedly increased postprandial plasma CCK release (P<0.001) while distinctly reducing postprandial PP levels (P<0.01) as compared to placebo [8].
• SR 27897B (3 and 10 nM) caused 7.9- and 17.9-fold shifts in the CCK concentration-response curve and the apparent-log KB values for each concentration of antagonist were calculated to be 9.36 and 9.23 [11].
• Acini were stimulated by sulfated gastrin in the presence of SR 27897 (1.8 microM), blocking endogenous CCKA receptors [17].
• The activity of SR 27897, a potent and selective CCK-A vs CCK-B receptor antagonist (Ki = 0.2 nM on guinea-pig pancreas vs 2000 nM on rat brain) was studied on behavioural, electrophysiological and biochemical effects induced by peripheral or central injection of CCK-8S [9].
• CCK-induced pancreatic secretion was abolished by SR 27897 (15 nmol kg-1 min-1, 55 min) and reduced by PD 135158 (0.15 nmol kg-1 min-1, 55 min) [18].

Analytical, diagnostic and therapeutic context of Lintitript

• In summary, SR 27897 is a selective antagonist of CCKA receptors, is highly potent in animal models whatever the route of administration and has a long duration of action.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
• Gastric emptying was assessed in nine healthy male volunteers using a randomized, double blind, two-period crossover design with oral lintitript (15 mg 1 h prior to meal intake) or placebo on two different days [8].

References