The effects of
butorphanol were studied in assays of antinociception,
respiratory depression, sedation, diuresis and reinforcing effects in rhesus monkeys, and
opioid binding in monkey brain.
Butorphanol (0.003-0.1 mg/kg s.c.) was effective in the warm-water tail withdrawal assay in 50 degrees C water but not in 55 degrees C. Over a similar dose range,
butorphanol caused substantial
respiratory depression, without an obvious plateau. Constrained
quadazocine apparent pA2 analysis on the respiratory depressant and antinociceptive effects of
butorphanol yielded different values between the two assays (
respiratory depression pA2 = 6.61; antinociception pA2 = 8.26).
Butorphanol (0.1 mg/kg) antagonized the antinociceptive effects of
etonitazene in 55 degrees C water, but caused a nonparallel leftward shift in the U50,488 dose-effect curve; both effects were probably due to
butorphanol's intermediate efficacy at
mu receptors.
Butorphanol (0.0001-0.003 mg/kg per injection i.v.) was self-administered; unlike other mu
opioid agonists, its maximum effect was depressed after pretreatment with
quadazocine (0.01-1.0 mg/kg).
Butorphanol (0.003-0.32 mg/kg) was devoid of substantial
sedative or muscle relaxant effects, as measured by observational rating scales.
Butorphanol (0.01-0.1 mg/kg s.c.), unlike U50,488 (0.01-0.32 mg/kg) did not cause diuresis. Kappa agonist or antagonist effects of
butorphanol were not detected in the present studies. This profile is consistent with
butorphanol's binding characteristics in rhesus monkey brain which indicated 12-fold mu:kappa selectively and 34-fold mu:delta selectivity.