The effect of fedotozine on visceral hypersensitivity was evaluated in conscious rats. One hour after colonic irritation (0.6% acetic acid intracolonically), a 30 mmHg colonic distension was applied for 10 min. Irritation increased the number of abdominal contractions induced by colonic distension (23.4 +/- 4.1 versus 4.8 +/- 1.4 in saline-treated rats, P < 0.001). Facilitation of colonic pain was reversed in a dose-dependent manner by fedotozine ((+)-(-1R1)-1-phenyl-1-[(3,4,5-trimethoxy)benzyloxymethyl]-N ,N-dimethyl-n-propylamine), (+/-)-U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl]cyclohexyl)benzen eacetamide) and morphine (respective ED50 values 0.67, 0.51 and 0.23 mg/kg s.c.). The kappa-opioid receptor antagonist, nor-binaltorphimine, abolished the effects of fedotozine and (+/-)-U-50,488H but not those of morphine. Low doses of naloxone (30 microg/kg s.c.) blocked the effect of morphine but not of fedotozine or (+/-)-U-50,488H. After intracerebroventricular administration, morphine was very potent (ED50 1.7 microg/rat), (+/-)-U-50,488H poorly active (58% of antinociception at 300 microg/rat) and fedotozine inactive up to 300 microg/rat. These results show that fedotozine blocks hypersensitive visceral pain by acting on peripheral kappa-opioid receptors in animals.

1997-01-01·Cell Injury and Protection in the Gastrointestinal Tract

Involvement of Corticotropin Releasing Factor (CRF) and Vasopressin (AVP) in Stress-Induced Exacerbation of Experimental Colitis in Rats

作者: J. Moré ; J. Louis Junien ; L. Buéno ; J. Fioramonti ; M. Gué ; C. Del Rio-Lacheze

Stress is supposed to be associated with exacerbation of inflammatory bowel diseases. Furthermore, stress-induced immune suppression is supposed to be mediated by activation of the hypothalamo—pituitary—adrenal (HPA) axis. This study was performed to evaluate the role of the key HPA modulator factors, corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in stress-induced exacerbation of colitis in rats chronically equipped with intracerebroventricular cannula.

1997-01-01·Life Sciences3区 · 医学

Reversal by K-agonists of peritoneal irritation-induced ileus and visceral pain in rats

3区 · 医学

Article

作者: P.J.M. Rivière ; F. Angel ; S.G. Dahl ; J.L. Junien ; X. Pascaud ; E. Chevalier ; N. Friese

Peritoneal irritation in rats induced by i.p. administration of acetic acid produces abdominal contractions reflecting visceral pain, and gastrointestinal ileus characterized by inhibition of gastric emptying and small intestine transit. In this study, gastric emptying (GE) and intestinal transit, calculated by the geometric center (GC) method, were estimated using a test meal labeled with 51Cr-EDTA. Visceral pain was assessed by counting abdominal contractions. Acetic acid produced abdominal contractions (80.8 +/- 3.3) and inhibition of GE (-54%) and GC (-63%) during the test-period. The kappa-opioid receptor agonists, CI-977 (+/-)-U-50,488H, (+/-)-bremazocine, PD-117,302, (-)-cyclazocine, and U-69,583, reversed abdominal contractions and inhibitions of gastrointestinal transit in a dose-related manner. The mu-opioid receptor agonists and potent analgesics, morphine and fentanyl did not restore normal gastric emptying and intestinal transit. These data suggest that selective kappa-opioid receptor agonists might be used to treat abdominal pain associated with motility and transit impairment during postoperative ileus.

100 项与 Institut de Recherche Jouveinal SA 相关的药物交易

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100 项与 Institut de Recherche Jouveinal SA 相关的转化医学

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