(604) Co‐Activation of Substance P And Opioid Receptors with The Novel Combinatorial Peptide, ESP7

Aim of Investigation: The co‐administration of several medications with different pharmacological profiles has gained popularity as a means of overcoming tolerance and side effects to classical pain medications. Novel single molecules that possess multiple analgesic targets may offer the advantage of weaker side effects and delayed tolerance, and overcome the need to dose with separate medications. Previous research suggests that Substance P can slow the development of tolerance to the analgesic effects of morphine. As a result, in the present study we tested ESP7, a novel compound, which was designed to bind to both opioid and Substance P receptors. Methods: After Animal Research Committee approval, male Sprague‐Dawley rats (200g–250g) were implanted with chronic indwelling IT catheters (tips at T13‐L1). For measurement of the thermal antinociceptive properties of ESP7, the tail flick apparatus was employed (baseline latency approximately 3 sec, cutoff 10 sec). Responses were expressed as % maximum possible effects (%MPE): % MPE = (post‐treatment latency B baseline latency)/cut off time B baseline latency) × 100%. Results and Conclusions: We have previously shown that a hybrid peptide containing both beta‐casomorphin‐like and substance P‐like structural characteristics possessed an antinociceptive effect after intrathecal administration (2). The preliminary data on ESP7 are very promising. ESP7 at graded doses produces antinociceptive responses in the rat after daily repeated intrathecal administration. Naltrexone (HCL) blocks the effects of ESP7, indicating that the analgesia is opioid in nature. Intriguingly, no significant tolerance develops to ESP7 over a 5‐day period. The novel peptide may have potential therapeutic value for the treatment of acute and chronic pain. Acknowledgments: Department of Anesthesia funds; NIDA Grant 04128; and The Richard Saltonstall Charitable Foundation 1. Brantl, V, Teschemacher H,eds. Beta‐casomorphins and related peptides: recent developments. Weinheim: New York:VCH; 1994;113–118.