Nalbuphine.
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 Unlike pentazocine or buprenorphine, nalbuphine does not suppress the narcotic abstinence syndrome in partly-withdrawn morphine-dependent animals or man.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strong antagonist activity, analgesic-range doses of nalbuphine severely exacerbate the withdrawal syndrome in partly-withdrawn mice, monkeys and humans. Nalbuphine also precipitates a strong abstinence response in non-withdrawn morphine-dependent animals and man.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)
Schmidt
W K
WK
Tam
S W
SW
Shotzberger
G S
GS
Smith
D H
DH
Clark
R
R
Vernier
V G
VG
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003864:Depression, Chemical; D004192:Discrimination, Psychological; D004285:Dogs; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009020:Morphine / Q000009:adverse effects; D009266:Nalbuphine / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D009270:Naloxone / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012119:Respiration / Q000187:drug effects; D012646:Self Administration; D012894:Sleep Stages / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D019966:Substance-Related Disorders / Q000209:etiology
D000700:Analgesics; D009019:Morphinans; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; D009266:Nalbuphine