enkephalin--leucine-2-alanine and Constipation

The author proceeds from the belief that it is the dystrophic changes and disturbances in the regeneration of the intestinal epithelium that play a decisive role in the pathogenesis and morphogenesis of irritable intestinal syndrome and chronic non-infectious undefined colitis. The above alterations develop secondary to the action of harmful factors and disturbed trophic influences of neurohumoral systems of regulation during different stages of stress. At the same time the synthetic leu-enkefalin dalargin is endowed with a marked antistressor activity as well as ability to strikingly improve the regeneration of the epithelium. This was reason why therapeutic efficacy of dalargin has been given a trial in the above pathologies. Positive dynamics of symptoms of the conditions in question has been shown as well as of the histologic picture of colonic mucosa biopsies during the course of treatment of the above ailments with dalargin.

Topics: Biopsy; Chronic Disease; Colitis; Colon; Colonic Diseases, Functional; Constipation; Drug Evaluation; Enkephalin, Leucine-2-Alanine; Gastrointestinal Agents; Humans

Some in vivo agonist and antagonist properties of the putative k-compound bremazocine were characterized in rats. Bremazocine, at doses from 0.015-32 mg/kg i.p., delayed nociceptive reaction on a 55 degrees C hot-plate with a dose-response curve not readily fitting a single straight line; this effect was antagonized by high doses of naloxone. In the same rats bremazocine did not delay the intestinal transit of a charcoal meal fed 5 min earlier and prevented morphine-induced constipation. This antagonism appeared to be opioid-specific and competitive, with apparent pA2 value 8.56. Catatonia induced by etorphine (0.004 mg/kg s.c.) and constipation induced by etorphine (0.004 mg/kg s.c.) and D-Ala2-D-Leu5-enkephalin (0.1 mg/kg i.p.) were completely antagonized by bremazocine (0.03-8 mg/kg i.p.). Antinociception induced by morphine (10 mg/kg i.v.) and etorphine (0.004 mg/kg s.c.) was only partly prevented. Naloxone (1 mg/kg) and bremazocine (0.015-1 mg/kg i.p.) precipitated a withdrawal syndrome, evaluated as jumping frequency, in rats rendered dependent to morphine. These data suggest the involvement of more than one opioid receptor population in bremazocine action in vivo.

Topics: Analgesics; Animals; Benzomorphans; Catatonia; Constipation; Dose-Response Relationship, Drug; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Etorphine; Gastrointestinal Motility; Humans; Male; Morphinans; Morphine; Naloxone; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders