Effects of graded oral doses of meptazinol and pentazocine in comparison with placebo on experimentally induced pain in healthy humans

The opioid agonist/antagonist meptazinol has proven to exert significant analgesia in a series of painful conditions. This study investigated the effects of single oral doses of meptazinol 100, 200, and 400 mg in comparison with pentazocine 50 and 100 mg and with placebo on experimentally induced pain. In addition, the side effect profiles were assessed. Twenty‐four healthy subjects participated each in six experiments in which they received, in random double‐blind fashion, each of the treatments. Every experiment comprised 10 series of measurements, two before and eight after drug administration, carried out at 30 min intervals. Meptazinol produced significant dose‐ related increases of threshold and tolerance to electrically and thermally induced pain. Meptazinol 400 mg was significantly superior to placebo in all pain measures and proved as effective as pentazocine 50 and 100 mg, which yielded about equal effects. Meptazinol 200 mg was significantly weaker than pentazocine 50 mg and differed significantly from placebo only in its effects on pain tolerance. Meptazinol did not cause any severe side effects or systematic alterations of respiration, blood pressure, heart rate and central nervous functions. Pentazocine caused a higher number and more severe side effects, one subject reporting severe dysphoria after pentazocine 100 mg. The results give further evidence that meptazinol is well suited to replace other opioid analgesics compromised by a high incidence of adverse effects.