Pharmacodynamics +<unk>  at opioid receptors Compound Affinities () Ratios Refs MOR:DOR:KOR<unk>  1.1 nM1.4 nM 16 nM67.5 nM 12 nM2.5 nM 1:15:111:48:1.8 (−)-Naloxone 0.559 nM0.93 nM 36.5 nM17 nM 4.91 nM2.3 nM 1:65:91:18:2 (+)-Naloxone 3,550 nM>1,000 nM 122,000 nM>1,000 nM 8,950 nM>1,000 nM 1:34:3<unk>  is a lipophilic compound that acts as a non-selective and competitive opioid receptor antagonist. The pharmacologically active isomer of<unk>  is (−)-naloxone.<unk> 's binding affinity is highest for the μ-opioid receptor (MOR), then the δ-opioid receptor (DOR), and lowest for the κ-opioid receptor (KOR);<unk>  has negligible affinity for the nociceptin receptor. If<unk>  is administered in the absence of concomitant opioid use, no functional pharmacological activity occurs, except the inability of the body to combat pain naturally. In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on<unk> . The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opioid receptors within the brain (a competitive antagonist, not a direct agonist), thereby preventing the action of both endogenous and xenobiotic opioids on these receptors without directly producing any effects itself. A single administration of<unk>  at a relatively high dose of 2 mg by intravenous injection has been found to produce brain MOR blockade of 80% at 5 minutes, 47% at 2 hours, 44% at 4 hours, and 8% at 8 hours. A low dose (2 μg/kg) produced brain MOR blockade of 42% at 5 minutes, 6% at 2 hours, 33% at 4 hours, and 10% at 8 hours. Intranasal administration of<unk>  via nasal spray has likewise been found to rapidly occupy brain MORs, with peak occupancy occurring at 20 minutes, peak occupancies of 67% at a dose of 2 mg and 85% with 4 mg, and an estimated half-life of occupancy disappearance of approximately 100 minutes (1.67 hours). Pharmacokinetics When administered parenterally (non-orally or non-rectally, e.g., intravenously or by injection), as is most common,<unk>  has a rapid distribution throughout the body. The mean serum half-life has been shown to range from 30 to 81 minutes, shorter than the average half-life of some opiates, necessitating repeat dosing if opioid receptors must be stopped from triggering for an extended period.<unk>  is primarily metabolized by the liver. Its major metabolite is<unk> -3-glucuronide, which is excreted in the urine. For people with liver diseases such as alcoholic liver disease or hepatitis,<unk>  usage has not been shown to increase serum liver enzyme levels.<unk>  has low systemic bioavailability when taken by mouth due to hepatic first-pass metabolism, but it does block opioid receptors that are located in the intestine.
Naloxone
Esketamine
Eptazocine
Pentazocine
Flumazenil
Nalorphine
Ephedrine
Alfentanil