DOSE-RESPONSE INHIBITION OF RAT COMPOUND NERVE ACTION-POTENTIAL BY DEXTROPROPOXYPHENE AND CODEINE COMPARED TO MORPHINE AND COCAINE INVITRO

1. The effects of dextropropoxyphene hydrochloride (dextropropoxyphene) codeine phosphate (codeine), morphine hydrochloride (morphine), and cocaine hydrochloride (cocaine) on the compound action potentials (cAP) of the rat phrenic nerve were studied in vitro. 2. Dextropropoxyphene, cocaine, codeine and morphine depressed the cAP in a reversible, dose-dependent way. After 60 min exposure to the drugs, dextropropoxyphene, inhibited the cAP between 0.025 and 0.5 mM, cocaine between 0.01 and 5 mM, codeine between 0.1 and 10 mM and morphine between 0.5 and 70 mM. The inhibition caused by 5 mM morphine could not be reversed by naloxone. 3. Dextropropoxyphene demonstrated the most potent cAP inhibition compared to the other drugs tested. The observed dose range for the inhibition of the cAP of rat phrenic nerve includes that observed after intoxications with dextropropoxyphene (0.004-0.06 mM) in the clinic. 4. For all other drugs tested the present observed dose ranges are much greater than the plasma concentrations previously reported after therapeutic use and intoxication. © 1990.