dextromethorphan and Hypersensitivity

Acute studies suggested a therapeutic benefit for fundus-relaxing drugs in functional dyspepsia (FD) with visceral hypersensitivity (VH) to gastric distention or impaired accommodation (IA), but long-term studies are lacking. R-137696 is a serotonin-1A (5-HT(1A)) receptor agonist which relaxes the proximal stomach in man. Our aim was to investigate the influence of R-137696 on symptoms in FD with VH or IA. Randomized, double-blind, placebo-controlled, parallel group study of 4 weeks R-137696 2 mg t.i.d. in FD with VH or IA. Symptoms were assessed using the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) total score and individual symptom subscales. Barostat studies were performed before and after 4 weeks of treatment. Fifty-three patients (33 VH and 20 IA), 18 men, mean age 40 +/- 13 years were recruited. Twenty-four received placebo and 29 received R-137696. In VH patients, both placebo and R-137696 improved total symptom scores, with a tendency for superiority of placebo (-1.12 vs-0.51, P = 0.07). Placebo was superior for the subscales of early satiety, bloating, fullness and discomfort (all P < 0.05). In IA, both placebo and R-137696 had no significant influence on total or individual symptom scores (-0.08 and -0.27). In VH, both placebo and R-137696 increased the discomfort volume, without a statistical difference between both arms (+120 and +164 mL). In IA, both placebo and R-137696 enhanced accommodation, without a statistical difference between both (+77 and +159 mL). Adverse events were similar for drug and placebo. A 4-week administration of the fundus-relaxing 5-HT(1A) agonist R-137696 failed to significantly improve symptoms, VH or gastric accommodation compared to placebo.

Topics: Adult; Cytochrome P-450 CYP2D6; Data Interpretation, Statistical; Dextromethorphan; Dose-Response Relationship, Drug; Dyspepsia; Female; Gastric Emptying; Gastric Fundus; Gastrointestinal Motility; Humans; Hypersensitivity; Male; Middle Aged; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Stomach

The analgesic properties of the noncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist dextromethorphan, available for clinical use as an antitussive, have been studied in the human capsaicin pain model to determine a possible clinical effect on pain due to central sensitization. Ninety milligrams dextromethorphan or vehicle was given orally to ten volunteers, each at two different occasions in a double-blind fashion, prior to an intradermal injection of 300 micrograms capsaicin. Ongoing pain, pain evoked by von Frey filament stimulation, and pressure pain thresholds were assessed before and after the capsaicin injection. The area in which von Frey filament stimulation evoked pain was mapped after the capsaicin injection. There were no significant group effects on ongoing pain, or on von Frey or pressure hypersensitivity. There was also no significant effect on the area of mechanical hypersensitivity. These results show that clinical doses of dextromethorphan do not effect ongoing or mechanically evoked pain after capsaicin injection.

Topics: Adult; Analgesics; Capsaicin; Dextromethorphan; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Female; Humans; Hypersensitivity; Male; Middle Aged; Pain; Stress, Mechanical

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