Pharmacodynamics +<unk>  Site Ki (nM) Species Ref ≥3,800 Human 960–2,400 Human 1,100–2,200 Human 5-HT2A 260 Human 5-HT2C 780 Human α1B 1,300 Human α2A 2,900 Human α2B 1,600 Human α2C 2,100 Human D2 20,000 Rat H1 9.6–16 Human H2 >100,000 Canine H3 >10,000 Human H4 >10,000 Human M1 80–100 Human M2 120–490 Human M3 84–229 Human M4 53–112 Human M5 30–260 Human 48,000–86,000 Rat 27,100 () Human Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.<unk> , while traditionally known as an antagonist, acts primarily as an inverse agonist of the histamine H1 receptor. It is a member of the ethanolamine class of antihistaminergic agents. By reversing the effects of histamine on the capillaries, it can reduce the intensity of allergic symptoms. It also crosses the blood–brain barrier and inversely agonizes the H1 receptors centrally. Its effects on central H1 receptors cause drowsiness. Like many other first-generation antihistamines,<unk>  is also a potent antimuscarinic (a competitive antagonist of muscarinic acetylcholine receptors) and, as such, at high doses can cause anticholinergic syndrome. The utility of<unk>  as an antiparkinson agent is the result of its blocking properties on the muscarinic acetylcholine receptors in the brain.<unk>  also acts as an intracellular sodium channel blocker, which is responsible for its actions as a local anesthetic.<unk>  has also been shown to inhibit the reuptake of serotonin. It has been shown to be a potentiator of analgesia induced by morphine, but not by endogenous opioids, in rats. The drug has also been found to act as an inhibitor of histamine N-methyltransferase (HNMT). + Overview of<unk>  targets and effects Biological target Mode of action Effect H1 receptor Inverse agonist Allergy reduction; Sedation receptors Antagonist Anticholinergic; Antiparkinson Sodium channels Blocker Local anesthetic Pharmacokinetics Oral bioavailability of<unk>  is in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration. The primary route of metabolism is two successive demethylations of the tertiary amine. The resulting primary amine is further oxidized to the carboxylic acid.<unk>  is metabolized by the cytochrome P450 enzymes CYP2D6, CYP1A2, CYP2C9, and CYP2C19. The elimination half-life of<unk>  has not been fully elucidated, but appears to range between 2.4 and 9.3 hours in healthy adults. A 1985 review of antihistamine pharmacokinetics found that the elimination half-life of<unk>  ranged between 3.4 and 9.3 hours across five studies, with a median elimination half-life of 4.3 hours. A subsequent 1990 study found that the elimination half-life of<unk>  was 5.4 hours in children, 9.2 hours in young adults, and 13.5 hours in the elderly. A 1998 study found a half-life of 4.1 ± 0.3 hours in young men, 7.4 ± 3.0 hours in elderly men, 4.4 ± 0.3 hours in young women, and 4.9 ± 0.6 hours in elderly women. In a 2018 study in children and adolescents, the half-life of<unk>  was 8 to 9 hours.
Diphenhydramine
Olopatadine
Ephedrine
Pseudoephedrine
Meclizine
Lofepramine
Dezocine
Molsidomine