No abstract

Scintigraphic techniques can measure sequentially gastric emptying, small bowel transit, and colonic transit in humans, and comparable methods for experimental studies in animals would be useful. We developed such a method in dogs and examined the effects of prokinetic drugs on regional transit. Two isotopes were given to fasting dogs. Polystyrene pellets labeled with99mTc were mixed in a can of dog food and 111In- labeled pellets were given in a gelatin capsule coated with a pH-sensitive polymer, designed to dissolve in the distal bowel. Gamma camera images were obtained for up to 24 h. Prokinetic drugs were given by intravenous injection. Duplicate baseline studies showed good agreement in seven dogs. In a second group ( n = 4), intra- and interanimal variabilities were established. Two novel prokinetic drugs (AU-116 and AU-130) accelerated small bowel and colonic transit. A simple noninvasive method for measuring whole gut transit in dogs was developed and validated. Two new prokinetics accelerated small bowel and colonic transit.

No abstract

The effects of systemic administration of morphine (4.0 mg kg-1) and clonidine (2.5-10.0 micrograms kg-1), as well as the peripherally active alpha 2-adrenoceptor agonist oxymetazoline (2.8-11.2 micrograms kg-1), were studied on the migrating myo-electric complexes (MMCs) of the small intestine in conscious, naive rats. Furthermore, the effects of naloxone (1.0 mg kg-1) and the peripherally acting opioid antagonist, methylbromide naloxone (1.0-2.0 mg kg-1) were studied on the MMCs in morphine-dependent animals. Similar doses of clonidine or oxymetazoline inhibited the MMCs of the small intestine, which suggests a peripheral site of action of clonidine. Since naloxone (1.0 mg kg-1) did not antagonize the effect of clonidine, and yohimbine (1.0 mg kg-1) failed to antagonize the effect of morphine on the MMC, the inhibitory effects on intestinal motility of clonidine and morphine are mediated through different receptors. Morphine-dependent rats showed a prolonged interval between activity fronts and decreased propagation velocity of the activity fronts. Both naloxone (1.0 mg kg-1) and methylbromide naloxone (1.0-2.0 mg kg-1) induced intense spiking activity and profuse diarrhoea. Clonidine (5.0-10.0 micrograms kg-1) as well as oxymetazoline (5.6-11.2 micrograms kg-1) given prior to naloxone prevented the intense spiking as well as the concomitant diarrhoea. We conclude that the potent inhibition of small intestinal myoelectric activity by alpha 2-adrenoceptor agonists is mainly executed via peripheral mechanisms. This effect may contribute to their beneficial action in morphine withdrawal diarrhoea, and partly underlie a general antidiarrhoeal action.(ABSTRACT TRUNCATED AT 250 WORDS)