Nalbuphine

Abstract

Nalbuphine is a potent analgesic with a low side effect and dependence profile in animals and man. Nalbuphine is distinguished from other agonist/antagonist analgesics in having greater antagonist activity and fewer behavioral effects at analgesic doses than pentazocine, butorphanol or buprenorphine. At equi-analgesic doses, nalbuphine is quantitatively similar to nalorphine in regard to its large ratio of antagonist to analgetic activity. Clinical studies have confirmed this balance of strong antagonist to analgesic activity. Nalbuphine has been shown to effectively antagonize the respiratory depressant activity of narcotic analgesics while concomitantly adding to their analgetic responses. Unlike nalorphine or pentazocine, nalbuphine produces few overt behavioral or autonomic effects in animals at doses over 300 times its analgesic range. These findings are confirmed by clinical results which show that nalbuphine produces few psychotomimetic effects, even at elevated dose levels, in contrast to nalorphine or pentazocine. Nalbuphine produces limited respiratory depression in animals and in man. Significant cardiovascular effects have not been found. Nalbuphine was found to produce significantly less inhibition of gastrointestinal activity than any of the clinically useful narcotic or agonist/antagonist analgesics tested in animals. Nalbuphine's analgetic effects are reversed by naloxone doses similar to those which reverse nalorphine's agonist effects. Results in this and other tests suggest that nalbuphine is primarily a kappa-agonist/mu-antagonist analgesic. Unlike pentazocine or buprenorphine, nalbuphine does not suppress the narcotic abstinence syndrome in partly-withdrawn morphine-dependent animals or man. Rather, due to nalbuphine's strong antagonist activity, analgesic-range doses of nalbuphine severely exacerbate the withdrawal syndrome in partly-withdrawn mice, monkeys and humans. Nalbuphine also precipitates a strong abstinence response in non-withdrawn morphine-dependent animals and man. In post-addict humans, analgesic-range doses of nalbuphine are perceived as minimally morphine-like, but higher doses are judged to be progressively more nalorphine-like (i.e. dysphoric), which further limits nalbuphine's abuse potential in drug-seeking individuals. Primary dependence studies have demonstrated that physical dependence is possible at high dose levels that produce marked side effects. Other studies show that dependence is unlikely to be of significance within nalbuphine's usual analgesic range. Six-month studies in patients with chronic pain have confirmed that analgesic tolerance or physical dependence is uncommon.(ABSTRACT TRUNCATED AT 400 WORDS)

The Effects of Nalbuphine and Butorphanol Treatment on Cocaine and Food Self-Administration by Rhesus Monkeys

“…The duration of nalbuphine's an algesic action is 3 to 6 hours (Forbes et al 1984;Schmidt et al 1985). The plasma half-life of an analgesic dose of nalbuphine (10 to 20 mg) after intravenous adminis tration in healthy volunteers has been estimated at be tween 1.9 and 3.7 hours (Aitkenhead et al 1988); Jail Ion et al 1989;Lo et al 1987).…”

“…antagonist actions under some conditions. Nalbuphine and butorphanol each have K agonist activity (Jaffe and Martin 1990; Schmidt et al 1985), whereas buprenor phine has K antagonist activity (Jaffe and Martin 1990;…”

“…Nalbuphine and butorphanol were se lected for study since both are currently approved by the Food and Drug Administration for use as analgesics and the pharmacology of these compounds has been studied extensively (Errick and Heel 1983;Pachter and Evans 1985;Schmidt et al 1985). A second objective was to examine the extent to which differences in the putative opioid receptor affm ities of these opioid mixed agonist-antagonists might influence their effects on co caine self-administration.…”

“…Nalbuphine and butorphanol are from the morphinan series (Schmidt et al 1985;Woolverton and Schuster 1983) whereas buprenorphine is an oripavine derivative of thebaine (Lewis 1974;Lewis et al 1983). Both nalbuphine and butorphanol have partial � and K agonist activity (Dyk stra 1990; Woods and Gmerek 1985) as well as � an tagonist opiate receptor activity (Jaffe and Martin 1990;Schmidt et al 1985) but their relative receptor selectivity varies with the type of assay as well as the species stud ied (De Souza et al 1988;Dykstra 1990). The analgesic effects of these drugs may involve more than one opi oid receptor.…”

Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

“…The social, health and economic costs of substance dependence (SD) are high (Nutt et al 2010); yet the universal efficacy of currently available treatments is limited, and the mechanisms of action of such treatments are poorly understood (Sturgess et al 2011; Tiffany et al 2012). Naltrexone, an opioid receptor antagonist targeting particularly the mu‐opioid receptor (MOR) subtype (Verebey & Mule 1975; Schmidt et al 1985), has been shown in randomized controlled trials to be effective in alcohol dependence (AD) but may be more effective in some individuals or subgroups and not others (Streeton & Whelan 2001) (Anton 2008; Sturgess et al 2011). The current study aims to examine the effects of naltrexone on the neural network changes associated with SD, specifically in poly‐drug SD and AD.…”