desvenlafaxine-succinate and Stomach-Ulcer

Topics: Abdominal Pain; Adult; Anti-Inflammatory Agents, Non-Steroidal; Depressive Disorder; Desvenlafaxine Succinate; Drug Synergism; Duloxetine Hydrochloride; Duodenal Ulcer; Gastrointestinal Hemorrhage; Gastroscopy; Humans; Male; Melena; Methimazole; Naproxen; Selective Serotonin Reuptake Inhibitors; Stomach Ulcer

Desvenlafaxine succinate (DVS) is a novel serotonin and norepinephrine reuptake inhibitor. The aim of this study was to investigate the effects of DVS on visceral hypersensitivity and solid gastric emptying in a rodent model of gastric hyperalgesia. Twenty-eight gastric hyperalgesia rats and 20 control rats were used. Visceral sensitivity during gastric distention (GD) was assessed by recording of electromyogram (EMG) at pressures of 20, 40, 60, and 80 mmHg. DVS with doses of 1, 10, and 30 mg/kg were administrated by gavage, 5-HT1A antagonist (WAY-100635, 0.3 mg/kg) was given subcutaneously, and 5-HT2A antagonist (ketanserin, 1 mg/kg) was given intraperitoneally. The level of norepinephrine in plasma was measured by enzyme-linked immunosorbent assay. We found that 1) visceral hypersensitivity induced by acetic acid was validated. 2) DVS dose-dependently reduced visceral hypersensitivity in the gastric hypersensitivity rats. The EMG (% of baseline value without GD) during GD at 60 and 80 mmHg with DVS at a dose of 30 mg/kg were 119.4 ± 2.3% (vs. saline 150.9 ± 2.7%, P < 0.001) and 128.2 ± 3.2% (vs. saline 171.1 ± 2.4%, P < 0.001). Similar findings were observed at a dose of 10 mg/kg. DVS at a dose of 1 mg/kg reduced visceral hypersensitivity only during GD at 60 mmHg. 3) Neither WAY-100635 nor ketanserin blocked the effect of DVS on visceral sensitivity. 4) DVS at 30 mg/kg significantly increased plasma NE level (P = 0.012 vs. saline). 5) DVS at 30 mg/kg significantly delayed solid gastric emptying (P < 0.05 vs. saline). We conclude that DVS reduces visceral sensitivity in a rodent model of visceral hypersensitivity and delays solid gastric emptying. Caution should be made when DVS is used for treating patients.

Topics: Acetic Acid; Administration, Oral; Adrenergic Uptake Inhibitors; Animals; Cyclohexanols; Desvenlafaxine Succinate; Disease Models, Animal; Dose-Response Relationship, Drug; Electromyography; Gastric Emptying; Gastroparesis; Hyperalgesia; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Mechanotransduction, Cellular; Norepinephrine; Pain Measurement; Pain Threshold; Pressure; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin 5-HT1 Receptor Antagonists; Serotonin 5-HT2 Receptor Antagonists; Stomach; Stomach Ulcer