Bremazocine induces antinociception, but prevents opioid-induced constipation and catatonia in rats and precipitates withdrawal in morphine-dependent rats.
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.
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000627:therapeutic use*; D002389:Catatonia / Q000517:prevention & control*; D003248:Constipation / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D005048:Etorphine / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D008297:Male; D009019:Morphinans / Q000627:therapeutic use*; D009020:Morphine / Q000009:adverse effects; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D019966:Substance-Related Disorders
D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans; D009270:Naloxone; D005048:Etorphine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine; C027248:bremazocine