Effectiveness of Nantradol in Blocking Narcotic Withdrawal Signs Through Nonnarcotic Mechanisms

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.

A re‐evaluation of the role of α2‐adrenoceptors in the anxiogenic effects of yohimbine, using the selective antagonist delequamine in the rat

“…Yohimbine has a high affinity for 5-HTlA receptors (Winter & Rabin, 1992), possessing partial agonist activity (Arthur et al, 1993); such ligands are anxiogenic in rats tested in the elevated Xmaze (Moser, 1989). Other possible explanations for the anxiogenic action of yohimbine include a dual action at adrenoceptors and dopamine receptors ; the interaction of yohimbine with the benzodiazepine modulatory site on the GABAA receptor (Lal et al, 1983) has been discounted as an explanation of its anxiogenic effects (Pellow et al, 1985b).…”

Effects of fixed-ratio length on the development of tolerance to decreased responding by l-nantradol

“…/-Nantradol has potent analgesic effects (Johnson et al 1981 ;Jain et al 1981), it can block morphine-abstinence signs (Lal et al 1981 ;Jacob et al 1981), and it has effects like morphine on spinal reflexes (Gilbert 1981). None of these effects of/-nantradol is antagonized by naloxone or naltrexone, however, (Yaksh 1981;Gilbert 1981), and /-nantradol does not substitute for morphine in drug-discrimination tests (Lal et al 1981 ;Young et al 1981). A wide variety of previous experiments have studied behavioral tolerance to the effects of other cannabinoids, but very few have included the effects of/-nantradol.…”

Differential effects of opioid and nonopioid analgesics on conditional discriminations in pigeons

“…1980;Lal et al 1981 ;Young et al 1981) nor are their effects blocked by opioid antagonists (Fielding et al 1978;Gilbert 1981;Dykstra 1983). In the present investigation, the effects of these compounds were quite different from those produced by morphine.…”

“…The synthetic cannabinoid l-nantradol and the alpha-2 adrenergic agonist clonidine are structurally and pharmacologically different from morphine and other opioid analgesics, yet possess analgesic properties (Fielding et al 1978;Jain et al 1981;Johnson et al 1981) and suppress morphine-abstinence signs (Jacob et al 1981;Lal et al 1981 ;Distefano and Brown 1985).…”