Pharmacological properties of RPR 102681, a novel CCK-B receptor antagonist

hme, GA B; Piot, O.; Betschart, J.; Bertrand, Paul; Obinu, C; Pauchet, C; Chaillou, Philippe; Jeantaud, Bernadette; Boudeau, Philippe; Guyon, Claude; Manfr, F; Daug, V; Roques, B. P.; Martellotta, M.C.; Fratta, Walter; Dubroeuco, MC; Impérato, Assunta

doi:10.1097/00008877-199711000-00030

Cited by 2 publications

(5 citation statements)

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“…It is possible that future studies with larger sample sizes will demonstrate a dosedependent effect. Contrary to the increased intrasynaptic DA after the administration of RPR 102681 predicted by the animal study, 12 RPR 102681 briefly increased radiotracer binding in the caudate and the VS in humans with cocaine abuse and cocaine dependence, which makes it unlikely candidate as an agonist substitution medication for cocaine, but with a sample size of 4, these results may be spurious.…”

Section: Con Clus Ioncontrasting

confidence: 62%

“…38 Additionally, the metabolism of RPR 102681 may alter the cellular environment leading to transient externalization of DA D 2 receptors 39 resulting in temporarily increased BP ND s. An alternative hypothesis could be an increase in autoreceptor affinity of DA D 2 for [ 11 C]raclopride in the presence of RPR 102681. 8 Contrary to the increased intrasynaptic DA after the administration of RPR 102681 predicted by the animal study, 12 RPR 102681 briefly increased radiotracer binding in the caudate and the VS in humans with cocaine abuse and cocaine dependence, which makes it unlikely candidate as an agonist substitution medication for cocaine, but with a sample size of 4, these results may be spurious.…”

Section: Con Clus Ionmentioning

confidence: 88%

“…A selective non‐peptide antagonist of the CCK‐B receptors with high affinity for human receptors is orally bioavailable and readily penetrates the blood‐brain barrier and can be detected in rat brain as early as 15‐30 minutes after oral administration . Intraperitoneal administration of RPR 102681 stimulated DA release in the ventral striatum (VS) of rats, nearly tripling the baseline levels when given at the highest dose tested (20 mg/kg)…”

Section: Introductionmentioning

confidence: 99%

“…8 Repetitive cocaine administration activates the mesolimbic CCK system, 9 CCK-B receptor antagonists effectively reduced both cocaine consumption and cocaine withdrawal-associated anxiety in animal models of addiction. 10 A selective non-peptide antagonist of the CCK-B receptors with high affinity for human receptors 11,12 is orally bioavailable and readily penetrates the blood-brain barrier and can be detected in rat brain as early as 15-30 minutes after oral administration. 13,14 Intraperitoneal administration of RPR 102681 stimulated DA release in the ventral striatum (VS) of rats, nearly tripling the baseline levels when given at the highest dose tested (20 mg/kg).…”

Section: Introductionmentioning

confidence: 99%

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A cholecystokinin B receptor antagonist and cocaine interaction, phase I study

et al. 2018

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Section: Con Clus Ioncontrasting

confidence: 62%

Section: Con Clus Ionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A cholecystokinin B receptor antagonist and cocaine interaction, phase I study

et al. 2018

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“…To check whether gastrin/CCK is involved in the action of bacterial LPS on mucosal integrity, separate subgroups of rats were used, and the effects of inhibition of CCK 1 and CCK 2 receptors with loxiglumide and RPR-102681, respectively, on the protection and adaptation induced by LPS were examined. RPR-102681 is a novel, nonpeptide selective antagonist of the CCK 2 /gastrin receptor, which has been shown to display nanomolar affinity of about 2000-fold greater selectivity for CCK 2 than CCK 1 receptors (Bohme et al, 1997). Loxiglumide was a generous gift of Dr. Rovati (University of Milan, Italy), and RPR-102681 was purchased from Aventis (Strasbourg, France).…”

Section: Methodsmentioning

confidence: 99%

Involvement of Capsaicin-Sensitive Afferent Nerves and Cholecystokinin 2/Gastrin Receptors in Gastroprotection and Adaptation of Gastric Mucosa toHelicobacter pylori-Lipopolysaccharide

Brzozowski

Konturek²,

Moran³

et al. 2004

J Pharmacol Exp Ther

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Lipopolysaccharide (LPS) is one of the virulence factors in theHelicobacter pylori (Hp)-infected stomach, but it remains unknown whether single and prolonged pretreatment with Hp-LPS can affect the course of gastric damage induced by aspirin (ASA). We compared the effects of Hp-LPS with those induced by LPSs isolated from intestinal Bacteroides fragilis, Yersinia enterocolitica, and Campylobacter jejuni applied for 4 days on acute ASA-induced gastric lesions in rats. The area of ASAinduced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1␤, and tumor necrosis factor-␣ levels were examined. Single (once) or repeated (five times) i.p. injections of Hp-LPS (1 mg/kg) or intestinal LPSs failed to produce macroscopic gastric damage and did not affect the GBF when compared with vehicle. Hp-LPS injected repeatedly suppressed the gastric acid secretion, up-regulated leptin mRNA and protein, and increased plasma leptin and gastrin levels. Hp-LPS significantly reduced the ASA-induced gastric damage and the accompanying decline in the GBF, and these effects were significantly attenuated by capsaicin denervation and selective antagonism of cholecystokinin-B (CCK 2 ) receptors by RPR-102681 [N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido}-3 phenyl}-2 propronique] but not by loxiglumide, an antagonist of CCK 1 receptors. We conclude that 1) daily application of Hp-LPS enhances gastric mucosal resistance against ASA damage due to the increase of GBF and the expression and release of leptin and gastrin exerting trophic and gastroprotective effects, and 2) this enhanced resistance to ASA damage in Hp-LPS-adapted stomach is mediated by the sensory afferents and specific CCK 2 /gastrin receptors.Helicobacter pylori (Hp) is now generally accepted as a major cause of chronic gastritis and an important risk factor for peptic ulcer disease and gastric cancer (Warren and Marshall, 1983;Konturek et al., 1999), but it remains unknown whether the gastric mucosa is capable of adapting to repeated Hp insults and whether such Hp adaptation might alter the mucosal resistance to the injurious action of strong irritants.Various pathogenic factors originating from Hp have been implicated in the damaging effect of this bacterium on the gastric mucosa, the most important in addition to ammonia being cytotoxins released by Hp strains expressing the vacuolating cytotoxin A and cytotoxin-associated gene A proteins, Hp-derived lipopolysaccharides (Hp-LPSs), and the enhanced generation of reactive oxygen species (Megraud et al., 1992;Crabtree, 1996;Figura and Tabaqchali, 1996; Moran, 2001a,b). Hp-LPS exhibits a low immunological activity, and this property has been assumed to play an important role in the persistency of Hp infection in the human stomach (Moran, 2001a,b). Nevertheless, the deleterious action of LPS derived from Hp in the stomach includes an interaction of this endotoxin with laminin (Valkonen et al., 1994), its influe...

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Pharmacological properties of RPR 102681, a novel CCK-B receptor antagonist

Cited by 2 publications

References 0 publications

A cholecystokinin B receptor antagonist and cocaine interaction, phase I study

A cholecystokinin B receptor antagonist and cocaine interaction, phase I study

Involvement of Capsaicin-Sensitive Afferent Nerves and Cholecystokinin 2/Gastrin Receptors in Gastroprotection and Adaptation of Gastric Mucosa toHelicobacter pylori-Lipopolysaccharide

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