Antinociceptive effect of dihydroetorphine following various routes of administration: A comparative study with morphine

Using various routes of administration, the antinociceptive effects of dihydroetorphine (DHE) and morphine were measured in mice, Regardless of the route of systemic and local administration, DHE (1-20 mu g/kg, i.p.; 1-10 mu g/kg, s.c.; 1-10 mu g/kg, i.v.; 10-1000 mu g/kg, p.o.; 10-100 ng/mouse, intracerebroventricularly (i.c,v.); and 10-100 ng/mouse, intrathecally (i.t.)) and morphine (1-20 mg/kg, i.p.; 1-10 mg/kg, s.c.; 1-10 mg/kg, i.v.; 10-100 mg/kg, p.o.; 1-10 mu g/mouse, i.c.v.; and 0.5-3 mu g/mouse, i.t.) produced an antinociceptive effect in a dose-dependent manner, as evaluated by the tail pinch method. However, the duration of the antinociceptive effect of DHE was shorter than that of morphine. The efficacy ratio of the antinociceptive effect between DHE and morphine was approximately 1000 to 1500: 1 by parenteral administration (i.p., s.c., or i.v.) and about 100:1 by the oral route. Meanwhile, using direct application into the central nervous system (CNS) (i.c.v. or i.t.), the effect of DHE was only 10 to 20 times that of morphine. These data suggest that DHE has an ideal quality as an analgesic by systemic administration which is a more convenient application than local injection, since only a minimum dose of DHE is needed to induce suitable potency of antinociception, and the duration of the effect is short, Further, these unique characteristics of DHE might lead to the prevention of the development of dependence by avoiding accumulation of the drug in the CNS.