text: Pharmacology Promethazine, a phenothiazine derivative, is structurally different from the neuroleptic phenothiazines, with similar but different effects. Despite structural differences, promethazine exhibits a strikingly similar binding profile to promazine, another phenothiazine compound. Both promethazine and promazine exhibit comparable neuroleptic potency, with a neuroleptic potency of 0.5. However, dosages used therapeutically, such as for sedation or sleep disorders, have no antipsychotic effect. It acts primarily as a strong antagonist of the H1 receptor (antihistamine, Ki = 1.4 nM) and a moderate mACh receptor antagonist (anticholinergic), and also has weak to moderate affinity for the 5-HT2A, 5-HT2C, D2, and α1-adrenergic receptors, where it acts as an antagonist at all sites, as well. New studies have shown that promethazine acts as a strong non-competitive selective NMDA receptor antagonist, with an EC50 of 20 μM; which might promote sedation in addition with the strong antihistaminergic effects of the H1 receptor, but also as a weaker analgesic. It does not however affect the AMPA receptors.
  Another notable use of promethazine is as a local anesthetic, by blockage of sodium channels.
  Chemistry
  Solid promethazine hydrochloride is a white to faint-yellow,  practically odorless, crystalline powder. Slow oxidation may occur upon prolonged exposure to air, usually causing blue discoloration. Its hydrochloride salt is freely soluble in water and somewhat soluble in alcohol. Promethazine is a chiral compound, occurring as a mixture of enantiomers.
  History
  Promethazine was first synthesized by a group at Rhone-Poulenc (which later became part of Sanofi) led by Paul Charpentier in the 1940s.  The team was seeking to improve on diphenhydramine; the same line of medical chemistry led to the creation of chlorpromazine.