Analgesic effects of ethylketocyclazocine and morphine in rat and toad

Abstract

We have previously found rat and toad ( Bufo marinus ) brain to contain inverse ratios of benzomorphan-preferring ( κ σ ) and morphine-preferring (μ) opioid receptor types. The aim of the present study was to compare in vivo pharmacologic activity of a benzomorphan, ethylketocyclazocine (EKC) and morphine sulfate (MS) in rat and toad. Footshock intensity thresholds for eliciting locomotion were determined and dose-response curves for EKC and MS analgesia were obtained. Drugs were injected subcutaneously. In rats (high μ, low κ in brain), both compounds produced analgesia and displayed similar sensitivity to naloxone antagonism. The analgesti effects of EKC and MS may, therefore, be mediated by a common receptor type (μ) in this pain test in rats. In toads (high κ, low μ in brain), MS produced naloxone-reversible analgesia at doses 20-fold higher than were effective in rats. Toads did not display EKC analgesia at doses below those producing motor impairment. Moreover, 50-fold higher doses were required to produce such impairment in toads. Thirty minutes following subcutaneous injection of 3H-EKC, similar concentrations were found in rat and toad brain. Uptake into brain is probably not a factor in the behavioral resistance of toads to EKC.