Effectiveness of Nantradol in Blocking Narcotic Withdrawal Signs Through Nonnarcotic Mechanisms

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Abstract
Male rats were made narcotic dependent through continuous intravenous infusion of morphine. During withdrawal, nantradol, clonidine, and morphine were found to block withdrawal signs in a dose‐dependent manner. Almost complete alleviation of withdrawal occurred with nantradol or clonidine at 0.16 mg/kg and with morphine at 40 mg/kg. The effectiveness of morphine, but not of nantradol or clonidine, was reversed by naloxone. Likewise, in naive rats given castor oil, naloxone did not block the antidiarrheal effect of nantradol or clonidine. In order to compare possible subjective effects of nantradol with other antiwithdrawal drugs, naive rats were trained to discriminate either morphine, cyclazocine, or clonidine from vehicle by selecting different levers for reinforcement. Nantradol failed to produce any generalization to morphine, cyclazocine, or clonidine, suggesting that this drug does not produce central subjective effects like those of the training drugs. In additional testing in behavioral experiments, nantradol failed to produce any sign of anxiogenic activity.