PT  - JOURNAL ARTICLE
AU  - Gatch, M B
AU  - Negus, S S
AU  - Mello, N K
AU  - Archer, S
AU  - Bidlack, J M
TI  - Effects of the structurally novel opioid 14 alpha, 14' beta-[dithiobis [(2-oxo-2,1-ethanediyl)imino]]bis(7,8-dihydromorphinone) on schedule-controlled behavior and thermal nociception in rhesus monkeys.
DP  - 1996 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1282--1289
VI  - 278
IP  - 3
4099  - http://jpet.aspetjournals.org/content/278/3/1282.short
4100  - http://jpet.aspetjournals.org/content/278/3/1282.full
SO  - J Pharmacol Exp Ther1996 Sep 01; 278
AB  - The in vivo pharmacology of the structurally novel opioid 14 alpha, 14' beta-[dithiobis[(2-oxo-2,1-ethanediyl)imino]]bis(7,8-dihydromorphinon e) (TAMO) was examined in rhesus monkeys with assays of schedule-controlled behavior and thermal nociception. TAMO (0.032-1.8 mg/kg) produced dose-dependent decreases in response rates maintained under a fixed-ratio 30 schedule of food delivery (n = 3) and increases in tail-withdrawal latencies in a warm-water tail-withdrawal procedure (n = 3). Both the rate-decreasing and antinociceptive effects of TAMO (1.0 mg/kg) were maximal after 40 to 80 min and lasted at least 160 min. Pretreatment with the mu-selective opioid antagonist quadazocine (0.001-0.1 mg/kg) antagonized the effects of TAMO and shifted the TAMO dose-effect curves to the right. Schild analysis yielded in vivo apparent pA2 values (mean +/- S.E.M.) of 8.8 +/- 0.072 and 8.7 +/- 0.40 for quadazocine antagonism of the rate-decreasing and antinociceptive effects, respectively, of TAMO, which suggests that the effects of TAMO were mediated by mu-opioid receptors. In addition, quadazocine (0.1-1.0 mg/kg) reversed the behavioral effects of TAMO (1.0 mg/kg) when quadazocine was administered immediately after TAMO had attained its maximal effect. Twenty-four-hour pretreatment with 1.0 mg/kg TAMO did not significantly after the rate-decreasing or antinociceptive effects of fentanyl or the rate-decreasing effects of morphine. The dose-effect curve for morphine antinociception was shifted 4-fold to the right 24 hr after pretreatment with 1.0 mg/kg TAMO. However, 24-hr pretreatment with an equiactive dose of morphine (10.0 mg/kg) also produced a small (2-fold) but significant rightward shift in the dose-effect curve for morphine antinociception. Twenty-four-hour pretreatment with 1.8 mg/kg TAMO had no effect on the antinociceptive effects of U69,593 (0.0032-0.1 mg/kg). These results suggest that TAMO acts as a reversible mu agonist with a relatively slow onset and a duration of action and relative efficacy similar to those of morphine in rhesus monkeys. Twenty-four hours after TAMO administration, the highest doses of TAMO that could be safely administered produced little or no mu antagonist effects and no kappa antagonist effects.