Promethazine is listed as one of the drugs of highest anticholinergic activity in a study of anticholinergenic burden, including long-term cognitive impairment. 
Another notable use of promethazine is as a local anesthetic, by blockade of sodium channels. 
Extremely rare side effects include:
In 2009, the US Supreme Court ruled on a product liability case involving promethazine. Diana Levine, a woman suffering from a migraine, was administered Wyeth 's Phenergan via IV push. The drug was injected improperly, resulting in gangrene and subsequent amputation of her right forearm below the elbow. A state jury awarded her $6 million in punitive damages.
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. 
As of July 2017 it was marketed under many brand names worldwide: Allersoothe, Antiallersin, Anvomin, Atosil, Avomine, Closin N, Codopalm, Diphergan, Farganesse, Fenazil, Fenergan, Fenezal, Frinova, Hiberna, Histabil, Histaloc, Histantil, Histazin, Histazine, Histerzin, Lenazine, Lergigan, Nufapreg, Otosil, Pamergan, Pharmaniaga, Phenadoz, Phenerex, Phenergan, Phénergan, Pipolphen, Polfergan, Proazamine, Progene, Prohist, Promet, Prometal, Prometazin, Prometazina, Promethazin, Prométhazine, Promethazinum, Promethegan, Promezin, Proneurin, Prothazin, Prothiazine, Prozin, Pyrethia, Quitazine, Reactifargan, Receptozine, Romergan, Sominex, Sylomet, Xepagan, Zinmet, and Zoralix. 
On September 9, 2009, the FDA required a boxed warning be put on promethazine for injection, stating the contraindication for subcutaneous administration. The preferred administrative route is intramuscular, which reduces risk of surrounding muscle and tissue damage. 
It is also marketed in many combination drug formulations:
Some documented side effects include:
The case was appealed to the Supreme Court on grounds of federal preemption and substantive due process.  The Supreme Court upheld the lower courts' rulings, stating that "Wyeth could have unilaterally added a stronger warning about IV-push administration" without acting in opposition to federal law.  In effect, this means drug manufacturers can be held liable for injuries if warnings of potential adverse effects, approved by the US Food and Drug Administration (FDA), are deemed insufficient by state courts.
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 has a variety of medical uses, including:
Because of potential for more severe side effects, this drug is on the list to avoid in the elderly.  In many countries (including the US and UK), promethazine is contraindicated in children less than two years of age, and strongly cautioned against in children between two and six, due to problems with respiratory depression and sleep apnea. 
Promethazine is a first-generation antihistamine of the phenothiazine family. The drug has strong sedative and weak antipsychotic effects. It also reduces motion sickness and has antiemetic (Histamine H1 receptors but it does not block the production of histamine ) and anticholinergic properties. In some countries it is prescribed for insomnia when benzodiazepines are contraindicated. It is available in many countries under many brand names.   Promethazine was developed in the mid 1940s when a team of scientists from Rhône-Poulenc laboratories were able to synthesize it from phenothiazine. 
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 H 1 receptor ( antihistamine ) and a moderate mACh receptor antagonist ( anticholinergic ),  and also has weak to moderate affinity for the 5-HT 2A,  5-HT 2C,  D 2,   and α 1 -adrenergic receptors,  where it acts as an antagonist at all sites, as well.Promethazine