Pharmacodynamics Opioid receptor blockade +<unk>  at human opioid receptors Affinities () Ratios Refs MOR:KOR:DOR 0.24 nM 0.083 nM 16 nM 3:1:193 0.3 nM 0.3 nM 7.3 nM 1:1:24<unk>  acts as an inverse agonist of the μ-opioid receptor (MOR) (Ki = 0.24 nM) and as a weak partial agonist (Ki = 0.083 nM; Emax = 20–30%) of the κ-opioid receptor (KOR), with similar binding for these two receptors but a several-fold preference for the KOR. In another study however,<unk>  had approximately equal affinity for the MOR and KOR. In vivo evidence indicative of KOR activation, such as elevation of serum prolactin levels due to dopamine suppression and increased hypothalamic–pituitary–adrenal axis activation via enhanced adrenocorticotropic hormone and cortisol secretion, has been observed in humans and animals. Side effects typical of KOR activation such as hallucinations and dissociation have also been observed with<unk>  in human studies. It is thought that<unk>  activation of KOR may produce dysphoria and anxiety. In addition to MOR and KOR binding,<unk>  also possesses some, albeit far lower affinity for the δ-opioid receptor (DOR) (Ki = 16 nM), where it behaves as an antagonist.<unk>  is structurally related to naltrexone and differs from it by substitution of the ketone group at the C6 position of naltrexone with a methylene group (CH2). It binds to the MOR with similar affinity relative to naltrexone, but binds "somewhat more avidly" to the KOR and DOR in comparison.<unk>  with a single 1 mg dose by intravenous injection has been found to produce brain MOR blockade of 99% at 5 minutes, 90% at 2 hours, 33% at 4 hours, and 10% at 8 hours. A lower dose of 1 μg/kg intravenously resulted in brain MOR blockade of 52% at 5 minutes, 33% at 2 hours, 47% at 4 hours, and 26% at 8 hours. With oral administration, peak brain MOR occupancy of 87 to 100% was found after 3 hours with single or repeated dosing of<unk> . At 26 hours (1.1 days) post-administration, brain MOR occupancy was 83 to 100%; at 50 hours (2.1 days), it was 48 to 72%; and at 74 hours (3.1 days), it was 12 to 46%. The half-time of<unk>  occupancy of brain MORs is about 29 hours and is much longer than with naloxone. Substantial brain MOR occupancy occurs with<unk>  even when blood levels of<unk>  are very low. The prolonged brain MOR occupancy of<unk>  may be due to slow dissociation of<unk>  from MORs consequent to its high MOR affinity. Metabolism<unk>  is extensively metabolized in the liver, mainly by conjugation with glucuronic acid and also by N-dealkylation. Less than 5% of the dose is excreted unchanged. The glucuronide metabolite is entirely inactive, while the N-dealkylated metabolite has minimal pharmacological activity.
Nalmefene
Tebentafusp
Alcaftadine
Desloratadine
Rupatadine
Loratadine
Quifenadine
Titermax