thebaine and Disease-Models--Animal

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D.. In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil.. Methyl-orvinol (10. Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Abdominal Pain; Analgesics; Analgesics, Opioid; Animals; Colon; Diarrhea; Disease Models, Animal; Gastrointestinal Motility; Gastrointestinal Transit; Irritable Bowel Syndrome; Male; Mice; Mice, Inbred BALB C; Muscle Contraction; Muscle, Smooth; Naloxone; Naltrexone; Receptors, Opioid; Thebaine

In this study, we synthesized some novel N-(tetrazol-1H-5-yl)-6,14-endoethenotetrahydrothebaine 7α-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as potential analgesic agents. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C NMR, 2D NMR, and high-resolution mass spectral data. The analgesic activity was evaluated by a rat-hot plate test model and a rat tail-flick model. Compound 12 showed analgesic activity higher than that of morphine. In addition to a histopathological and biochemical evaluation, the LD₅₀ dose for the most active compound 12 was determined.

Topics: Analgesics; Animals; Disease Models, Animal; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Morphine; Oxadiazoles; Pain; Rats; Rats, Wistar; Thebaine; Thiadiazoles

Topics: Animals; Antitussive Agents; Chlorobenzenes; Codeine; Cough; Disease Models, Animal; Dogs; Electric Stimulation; Electrodes; Electrodes, Implanted; Guinea Pigs; Methyl Ethers; Morphine; Mucous Membrane; Piperidines; Pyridines; Reflex; Species Specificity; Thebaine; Time Factors; Trachea