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• W2073276286 abstract "Abstract The effects of fedotozine, (+)-(1R)-1-phenyl-1-[(3,4,5-trimethoxy)benzyloxymethyl]-N,N- dimethyl-n-propylamine, on motility of the antrum and small intestine were investigated in dog. In fasted dogs, following i.v. administration, fedotozine at 1 and 2 mg kg−1 stimulated and at 5 mg kg−1 inhibited antral motility. Between 1 to 5 mg kg−1, fedotozine exhibited a sustained and potent stimulatory effect on the small intestine inducing 1 to 4 phases III of the migrating motor complex (MMC) lasting up to 32 min in the duodenum and migrating to the jejunum. Following oral administration, fedotozine at 2–5 and 5 mg kg−1 constantly stimulated both antrum and small intestinal motility. In fed dogs, fedotozine i.v. (2 mg kg−1) increased antral motility and induced phase III of MMC in the place of postprandial pattern. Naloxone (0.3 mg kg−1 i.v.) and naloxone methylbromide (2 mg kg−1 i.v.) inhibited the stimulatory effects of fedotozine on gastrointestinal motility indicating a peripheral opiate site of action of the drug whereas phentolamine, hexamethonium, propranolol and methysergide were inactive. In-vitro fedotozine showed submicromolar affinity for opiate receptors with a weak specificity for the μ-receptors in guinea-pig brain and myenteric plexus preparations. Plasma concentrations in dogs receiving fedotozine administered orally at 2.5 mg kg−1 (and in all dogs except one at 5 mg kg−1) were below the detection limit (&lt; 20 ng g−1). In contrast, tissue concentrations in the muscle and mucosal layers of the gut were above 1 μg g−1. Concentrations in gastric juice after i.v. injection of fedotozine were 10 to 20 times higher than in the plasma, indicating passage of the drug from the blood into the lumen. These results indicate that fedotozine between 1 to 5 mg kg−1 orally or i.v. stimulates gastrointestinal motility in dog through peripheral opiate receptors. This peripheral activity is related to a high distribution of the drug at the target organ." @default.
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• W2073276286 date "1990-08-01" @default.
• W2073276286 modified "2023-10-16" @default.
• W2073276286 title "Effects of Fedotozine on Gastrointestinal Motility in Dogs: Mechanism of Action and Related Pharmacokinetics" @default.
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• W2073276286 doi "https://doi.org/10.1111/j.2042-7158.1990.tb07056.x" @default.
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