Pharmacology
Promethazine, a phenothiazine derivative, is structurally different from the neuroleptic phenothiazines, with similar but different effects. It acts primarily as a strong antagonist of the H1 receptor (antihistamine) 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; 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 early 1940s. The team was seeking to improve on diphenhydramine; the same line on medical chemistry led to the creation of chlorpromazine.
Promethazine is a first-generation antihistamine and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people who are agitated or anxious. Promethazine is available by mouth in syrup or tablet dosage forms, as a rectal suppository, or by injection into a muscle.Common side effects of promethazine include confusion and sleepiness; consumption of alcohol or other sedatives can make these symptoms worse. It is unclear if use of promethazine during pregnancy or breastfeeding is safe for the baby. Use of promethazine is not recommended in those less than two years old, due to potentially negative effects on breathing. Use of promethazine by injection into a vein is not recommended, due to potential skin damage. Promethazine is in the phenothiazine family of medications.Promethazine was made in the 1940s by a team of scientists from Rhône-Poulenc laboratories. It was approved for medical use in the United States in 1951. It is a generic medication and is available under many brand names globally. In 2019, it was the 174th most commonly prescribed medication in the United States, with more than 3 million prescriptions. Medical uses
Promethazine has a variety of medical uses, including:

Sedation
For nausea and vomiting associated with anesthesia or chemotherapy. It is commonly used postoperatively as an antiemetic. The antiemetic activity increases with increased dosing; however, side effects also increase, which often limits maximal dosing.