Salutary and detrimental effects of the (+)- and (-)enantiomers of meptazinol in anesthetized rats subjected to hemorrhagic shock.

The effects of the two enantiomers of the opioid mixed agonist-antagonist meptazinol on mean arterial pressure (MABP), heart rate (HR), and survival time were investigated in pentobarbitone-anesthetized rats subjected to hemorrhagic shock. Following intravenous administration of (+)meptazinol (0.5 mg kg-1) to shocked animals (MABP, 30.0 +/- 0.2 mm Hg), there was significant and gradual elevation of MABP, which at the time the experiment was terminated did not differ significantly from preshock values. In addition, survival was prolonged by up to 7 days. Paradoxically, similar doses of (-)meptazinol produced further falls in MABP, significantly so at 60 min posttreatment. Likewise, the drug produced a slow progressive and significant decline in HR which culminated in premature death (mean survival time, 74.3 +/- 5.9 min, compared with a control value of 104.4 +/- 8.8 min; p less than 0.05). Our results demonstrate that the two enantiomers of meptazinol have opposing effects on hemorrhagic shock sequelae in the rat. It is surprising, in view of its known opioid antagonistic properties, that (-)meptazinol exerted a detrimental effect.