Mechanism of action of suprofen, a new peripheral analgesic, as demonstrated by its effects on several nociceptive mediators

Abstract

Suprofen is a new potent, orally effective non-narcotic analgesic agent having a potent inhibitory action on prostaglandin (PG) biosynthesis. Recent experiments have shown that suprofen inhibits uterine hyperactivity induced by the physiological substances, arachidonic acid, bradykinin (BK) and PGF2 alpha. The present study explores the possibility that the analgesic activity of suprofen may involve multiple mechanisms of interaction with PGs, inhibiting synthesis at low doses and with higher doses possibly directly interacting with PGs and other physiological mediators of nociception at a common site. Experiments in mice have shown that suprofen antagonizes abdominal stretching induced by the physiological precursor of PG release, arachidonic acid (ED50 = 0.07 mg/kg, p.o.), and by the nociceptive agents acetylcholine (ACh) (ED50 = 1.7 mg/kg, p.o.), BK (ED50 = 65 mg/kg, p.o.) acetic acid (HAC) (H+ ion; ED50 = 4.6 mg/kg, p.o.), and PGE2, itself (ED50 = 20.2 mg/kg, i.p.). In rabbits, i.a. administered suprofen (ED50 = 0.98 mg/kg) blocked the reflex discharge of spinal sensory neurons evoked by BK (2 to 8 micrograms, i.a.). The analgesic activity of suprofen may involve multiple mechanisms of interaction with PGs and other mediators, including BK; suprofen blocks the nociceptive actions of PGs by inhibiting their formation, via the cyclooxygenase pathway, and possibly at PG sites of action, probably at peripheral nerve endings.