Analgesia duration and physical dependence in mice after a single injection of three heroin salts and morphine sulphate in various vehicles.

Mice were given single s.c. injections of morphine sulphate (M.S.), heroin hydrochloride (H.HCl) and the sparingly-soluble diheroin pamoate (H.Pam) and 3,5-di-tert-butyl-2,6-dihydroxybenzoate (H.Bnz) in three vehicles, saline, peanut oil, or a slow-release vehicle (SRV) and tested for analgesia by both the tail-clip and hotplate techniques. Duration of analgesia as assessed by the tail-clip method was always longer than that by the hotplate when equivalent doses were used in any vehicle. The H.Pam and H.Bnz salts significantly prolonged the analgesia: the mean duration in mice injected with equivalent amounts of heroin base was 3.0 hr for the group receiving heroin HCl in saline and 7.8 hr after H.Bnz in slow-release vehicle. An inverse relationship was evident between the degree of dissociation of H from the three salts, at pH 7.3 and their durations of analgesia in vivo. This was statistically significant (p less than 0.01) at the higher dose level. All mice were challenged with naloxone hydrochloride (1 mg/kg) 24 hr after the injection of each narcotic agonist preparation. The jumping behaviour elicited by naloxone was not consistently related to dose, salt form, or vehicle employed for the injection of agonists, but from 12.5 too 54.2% of all the mice did jump at that time. The durations of analgesia observed and the intensity of the jumping response correlated significantly with the mean number of jumps per mouse after the naloxone challenge.