Phenylmethylsulfonyl fluoride (PMSF) given systemically produces naloxone-reversible analgesia and potentiates effects of beta-endorphin given centrally.

Intraperitoneal (IP) injection of the serine proteinase inhibitor phenylmethylsulfonyl fluoride (PMSF) produced dose-dependent analgesia in Sprague-Dawley rats. AD50 was 2.9 +/- 1.4 (S.E.) mg kg-1, the analgesia was antagonized by naloxone but unaffected by atropine. PMSF significantly enhanced the analgesic effect of beta-endorphin (END) given by intracerebroventricular (ICV) infusion in rats, the enhanced END analgesia was naloxone-reversible. In Swiss-Webster mice the 24-hr LD50 value for PMSF was 215 +/- 55 mg kg-1 IP; autonomic and behavioral responses were similar to those seen in rats with ICV END. These results indicate that systemic PMSF can protect central endorphin(s) from enzymatic destruction. The significant analgesia, low toxicity, naloxone reversibility and minimal anticholinesterase effects suggest the use of PMSF as a parenteral analgesic.