Pharmacodynamics +<unk>  at opioid receptors Site Ref 0.89 nM 14 nM 47% 240 nM 2.2 nM 27 nM 81%<unk>  is a semisynthetic mixed agonist/antagonist opioid modulator of the phenanthrene or morphinan series. It is structurally related to the widely used opioid antagonists naloxone and naltrexone, and to the potent opioid analgesic oxymorphone.<unk>  binds with high affinity to the MOR and KOR, and has relatively low affinity for the DOR. It behaves as a moderate-efficacy partial agonist (or mixed agonist/antagonist) of the MOR and as a high-efficacy partial agonist of the KOR.<unk>  has weak or no affinity for the sigma receptor(s) (e.g., Ki > 100,000 nM).<unk>  is said to be more morphine-like at lower doses. However at higher doses, it produces more sedation, drunkenness, dysphoria, and dissociation. As such, its effects are dose-dependent. Such effects include sedation (21–36%), dizziness or vertigo (5%), lightheadedness (1%), anxiety (<1%), dysphoria (<1%), euphoria (<1%), confusion (<1%), hallucinations (<1%), depersonalization (1%), unusual dreams (<1%), and feelings of "unreality" (<1%).<unk>  is a potent analgesic. Its analgesic potency is essentially equivalent to that of morphine on a milligram basis, which is based on relative potency studies using intramuscular administration (Beaver et al. 1978). Oral administered<unk>  is reported to be three times more potent than codeine (Okun et al. 1982). Clinical trials studied single dose experimental oral immediate release<unk>  tablets for analgesic efficacy over a four- to six-hour time period following administration.<unk>  in the 15 to 60 mg range had similar analgesic effects to immediate release codeine in the 30 to 60 mg range (Kantor et al. 1984; Sunshine et al. 1983). Schmidt et al. (1985) reviewed the preclinical pharmacology of<unk>  and reported comparative data relative to other types of opioid compounds. The authors point out that the<unk>  moiety is approximately ten times more pharmacologically potent than the mixed opioid agonist/antagonist butorphanol on an "antagonist index" scale which quantitates the drug's ability to act both as an analgesic (via opioid KOR agonism) as well as a MOR antagonist. The opioid antagonist activity of<unk>  is one-fourth as potent as nalorphine and 10 times that of pentazocine. Pharmacokinetics The onset of action of<unk>  occurs within 2 to 3 minutes after intravenous administration, and in less than 15 minutes following subcutaneous or intramuscular injection. The elimination half-life of<unk>  is approximately 5 hours on average and in clinical studies the duration of analgesic activity has been reported to range from 3 to 6 hours.
Nalbuphine
Triazolam
Estazolam
Haloxazolam
Dezocine
Naltrexone
Remimazolam
Halazepam