Abstracts
1997 Digestive Disease Week

NMDA induces vomiting via a different mechanism than morphine.

M Hotokezaka, SP Patel, EP Mentis, BD Schirmer. Department of Surgery, University of Virginia Health Sciences Center. Charlottesville, VA.

The glutamate receptor agonist, NMDA, produces vomiting and slowing of gastric slow wave frequency in a pattern similar to morphine. We investigated whether the mechanism of NMDA action was mediated by similar pathways. Eight mongrel dogs underwent placement of seromuscular bipolar recording electrodes on the stomach and small intestine. After recovery from surgery, fasting dogs were given NMDA (1.5 mg/kg) i. v. during phase I of gastric motility. On subsequent test days, NMDA was administered after pretreatment with either atropine [ATR] (1mg/kg), the centrally acting opioid inhibitor naloxone [NAL] (0.1 mg/kg), or the periphally acting opioid inhibitor levallorphan [LEV] (0.1 mg/kg). Myoelectric activity patterns and vomiting were recorded. Data were analyzed by ANOVA and Fisher's exact test. Data are expressed as mean ± SEM, or #observed/ #studied:

                 NMDA      NMDA+ATR      NMDA+NAL      NMDA+LEV
 Emesis          7/8         5/8           8/8           4/8
    Gastric slow wave frequency (cycles/min)
 Time after NMDA
 Baseline       4.5±0.2     4.9±0.3       4.8±0.2       3.5±0.5
 4 min          3.5±0.5     2.5±0.4*      3.0±0.4*      3.1±0.8
 5 min          3.3±0.3*    3.1±0.4*      3.4±0.3*      2.6±0.4
 10 min         5.0±0.1     5.0±0.2       4.9±0.1       4.1±0.4
 (* p<0.05 vs. Baseline)

Duodenal slow wave frequency showed no slowing after NMDA. Although LEV prevented a significant decrease in gastric slow wave frequency, it did not abolish emesis. NAL and ATR had no effect on either emesis or slow wave frequency. We conclude that the similar patterns of gastric myoelectric changes and emesis seen after both morphine and NMDA are mediated through different pathways.