ASSESSMENT OF THE RELATIVE INTRINSIC EFFICACY OF PROFADOL AND MEPERIDINE IN A PIGEON DRUG DISCRIMINATION PROCEDURE - RELEVANCE TO PARTIAL SUBSTITUTION PATTERNS

Substitution and antagonism patterns of butorphanol, meperidine and pr ofadol were examined in pigeons trained to discriminate either a 0.056 (low) or 0.18 (high) mg/kg dose of fentanyl from saline. In the low-d ose group, fentanyl, meperidine, profadol and butorphanol substituted completely (greater than or equal to 85% fentanyl-appropriate respondi ng) for the fentanyl stimulus. For fentanyl and butorphanol, complete substitution was obtained at doses that had little effect on rates of responding, whereas profadol substituted at doses that moderately decr eased rates and meperidine substituted at doses that markedly decrease d rates. Although naloxone antagonized the stimulus effects of meperid ine and profadol, it failed to alter their rate-decreasing effects. In the high-dose group, fentanyl and butorphanol substituted completely and meperidine and profadol partially (approximately 50% fentanyl-appr opriate responding) for the fentanyl stimulus. During antagonism tests , meperidine and profadol produced only small decreases (less than 15% ) in the percentage of fentanyl-appropriate responding produced by the training dose of fentanyl. Analysis of individual data indicated that meperidine and profadol produced three patterns of substitution and a ntagonism. In one subgroup of pigeons, meperidine and profadol substit uted completely for but failed to antagonize the fentanyl stimulus; in another, these opioids failed to substitute for but did antagonize th e fentanyl stimulus; and in another, these opioids failed to substitut e for or antagonize the fentanyl stimulus. In this latter subgroup, me peridine and profadol produced leftward shifts in the dose-effect func tion for the stimulus effects of fentanyl and butorphanol. The present findings suggest that the failure of meperidine and profadol to subst itute completely for the high-dose fentanyl stimulus was a direct cons equence of their rate-decreasing effects rather than low efficacy at t he mu receptor.