ABSTRACT
Nalmefene is an orally active opiate antagonist structurally related to naloxone and naltrexone. In this study using two different strains of mice (Swiss Cox and ICR), the antagonist activity of nalmefene given subcutaneously (sc) was quantified by determination of the apparent pA2 values against the antinociceptive activity (tail flick and hot plate tests) of morphine given sc or intrathecally (lumbar spinal cord). The apparent pA2 values (constrained to a slope of -1) were 8.06 (7.79-8.33) in Swiss Cox mice and 7.81 (7.62-8.00) in ICR mice in the tail flick test with sc morphine. These values were larger than the corresponding value for naloxone in ICR mice, 7.35 (7.10-7.60). The hot plate test provided similar results: the apparent pA2 values for nalmefene with sc morphine were 8.14 (7.89-8.39) in Swiss Cox mice and 7.81 (7.65-7.97) in ICR mice, values which were different from naloxone 7.33 (7.23-7.42) in ICR mice. Apparent pA2 values for nalmefene with intrathecal morphine were not different from those for naloxone in the tail flick test. Thus, these sets of results suggest that it may be worthwhile to further determine whether systemic nalmefene might possibly possess an advantage over naloxone in antagonizing systemic side effects of morphine arising from local spinal morphine administration.
