TY - JOUR T1 - Effect of morphine and methadone acute treatment on immunological activity in mice: pharmacokinetic and pharmacodynamic correlates. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1112 LP - 1116 VL - 269 IS - 3 AU - R Pacifici AU - G Patrini AU - I Venier AU - D Parolaro AU - P Zuccaro AU - E Gori Y1 - 1994/06/01 UR - http://jpet.aspetjournals.org/content/269/3/1112.abstract N2 - This report describes the 24-hr time course of the immunomodulatory effects of an acute s.c. injection of morphine in C57BL6 mice, and correlates these effects with the drug's analgesic properties and serum levels. Acute morphine treatment had a biphasic effect on various immune parameters: there was an increase in in vitro phagocytosis and the killing of Candida Albican cells by peritoneal polymorphonuclear leukocytes 20 and 40 min after the injection of morphine, 20 mg/kg, when analgesia and serum morphine concentrations were at their peak. Interestingly, 24 hr after morphine administration (when antinociception and morphine blood levels were no longer detectable) these parameters underwent a marked reduction. Similarly, macrophage-mediated inhibition of tumor cells proliferation was first stimulated (at 20 and 40 min) and then depressed (at 24 hr). Splenic natural killer cell cytotoxicity, determined by standard 51Cr release from YAC-1 target cells, also was evaluated. No differences in natural killer activity was observed at any of the monitored time points. In addition, we evaluated the immunomodulatory effects of an acute injection of methadone (a synthetic narcotic compound) at a dose inducing the same degree of analgesia as morphine. None of the tested immunoparameters were affected by the administration of methadone, which indicates the different drug-sensitivity of immunological correlates in vivo. ER -