Degree and Duration of Reversal by Naloxone of Effects of Morphine in Conscious Subjects

Abstract

SummaryThe effects of intravenous naloxone on several of the actions of intravenous morphine (mean dose 30 mg/70 kg) were studied in six volunteer subjects. Naloxone produced a well defined reversal of the respiratory depression, analgesia, and miotic and subjective effects of the morphine. The agonist action of morphine outlasted the antagonist action of a single dose of naloxone. The effect of repeated doses of naloxone was also short-lived, but continuous infusions were effective in maintaining reversal. IntroductionIn conscious and anaesthetized subjects naloxone reverses the depressant effects of narcotics (Foldes et al., 1963(Foldes et al., , 1969Sadove et al., 1963). Hasbrouck (1971) showed the reversal of morphineinduced respiratory depression and electroencephalographical changes in the postoperative period. It has been suggested that naloxone may preserve the analgesic action of morphine while effectively reversing respiratory depression (Hasbrouck, 1971;Heisterkamp, 1972). Jasinski et al. (1968) showed that naloxone could antagonise the behavioural and pupillary effects of cyclazocine in addition to its respiratory depressant effect. The duration of action of naloxone has been claimed to be several hours (Jasinski et al., 1968), but other investigators have suggested that it is very much shorter (Hasbrouck, 1971;Fink et al., 1968;Evans et al., 1973).Naloxone is evidently an effective narcotic antagonist; its duration of action, however, and relative effect on analgesia and respiratory depression and on the subjective effects produced by narcotics are not yet clear. The antagonist properties of naloxone were therefore studied to elucidate these points.

An Introduction to the Endogenous Cannabinoid System

“…Evidence that acute responses to cannabis involves both agonism and antagonism of CB 1 receptor signaling is the observation that even repeated, very high doses of the CB 1 receptor antagonist, rimonabant, modestly attenuated the subjective measures of “high,” while substantially suppressing the tachycardia induced by cannabis (122). This contrasts to the rapid reversal of the subjective effects of morphine following the administration of naloxone (123). Similarly, oral rimonabant did not elicit a precipitated withdrawal syndrome in humans taking moderate doses of THC in a supervised environment (124).…”

Attenuation of the Antihypertensive Effect of Captopril by the Opioid Receptor Antagonist Naloxone

“…Reversal of opiate-induced respiratory depression by intravenous naloxone is both rapid and transient, lasting approximately 45 min (Evans et al, 1974). Also, blood naloxone levels fall quickly due to rapid distribution (Ngai et al, 1976).…”

A Comparison in Mice of Naloxone and Nalorphine as Antagonists to Neuroleptanalgesic Drugs

“…Naloxone is a more recently developed narcotic antagonist, now released for clinical use in this country. It is reported to be between 10 and 15 times more potent as an antagonist than is nalorphine (Hasbrouck, 1971) and, in addition, is devoid of significant agonist effects (Foldes, Duncalf and Kuwabara, 1969;Evans et al, 1974a).…”