R 62 818, a new analgesic: A comparative study with codeine

R 62 818 and codeine were studied in parallel, mainly in mice and rats. Three levels of analgesia were measured in mice using the hot plate test. ED50 values after sc administration were 6.20, 12.4, and 32.5 mg/kg with R 62 818 and 9.38, 18.7 and 32.5 mg/kg with codeine. In rats five levels of analgesic activity were evaluated, three in the acetic acidinduced writhing and two in the tail withdrawal reaction test. The oral ED50 values were: 2.71, 6.20, 12.4, 12.9, and 17.7 mg/kg with R 62 818 and 5.79, 8.17, 13.3, 24.8, and 69.3 mg/kg with codeine. In mice progressively more marked mydriasis was induced with R 62 818 at doses of 15.2, 23.0, and 52.9 mg/kg, with codeine at the much lower doses of 8.76, 11.5, and 26.4 mg/kg. Straub tail occurred with both compounds at 24.7 mg/kg. In contrast to codeine, R 62 818 did not reduce gastrointestinal motility. In rats various morphine-like effects (exopthalmos, blockade of pinna and cornea reflexes, muscle rigidity) were observed with both compounds, but with R 62 818 at much higher doses relative to the analgesic dose. In contrast to codeine, R 62 818 did not induce constipation. Naloxone reversed the analgesic and behavioral effects of an equipotent dose of both compounds with comparable effectiveness. R 62 818 protected animals from KCN-induced lethal shock, whereas codeine did not. Like other narcotic analgesics, codeine potentiated tryptamine lethality, whereas R 62 818 did not. The safety margins (LD50: lowest hot plate ED 50) in mice were 96.3 for R 62 818 and 21.9 for codeine, in rats (LD50: lowest tail withdrawal ED50) 81.8 for R 62 818 and 18.3 for codeine. R 62 818 appears to be a relatively more specific, slightly more potent and safer analgesic than codeine, with earlier peak effect and shorter duration of action. Its activity profile is not typical morphine-like.