The first antipsychotic drug is still on the WHO essential medicines list
Chlorpromazine, developed in 1950 and sold as Thorazine and Largactil, was the first antipsychotic to reach the market, and its arrival is counted among psychiatry's great advances. More than seventy years on it remains a cheap benchmark drug, on the WHO essential medicines list, and one of the world's most used schizophrenia treatments.
Chemically it belongs to the phenothiazines and is classed as a typical antipsychotic. Exactly how it works is not fully settled, but blocking dopamine receptors is thought to be central. It binds strongly to D2 receptors and, unusually for its class, to D1 receptors too. Blocking them first provokes neurons to release extra dopamine; over time production falls away and activity drops. Blockade in one brain pathway is believed to produce the antipsychotic effect, while blockade in another causes movement side effects. It also blocks serotonin and histamine receptors.
Its main job is treating psychoses such as schizophrenia and the manic phase of bipolar disorder. A 2014 Cochrane review of 55 trials found that, compared with placebo, it reduced relapse over six months to two years and improved symptoms and functioning. The same review described its side effects as severe and debilitating, rated the evidence very low quality, and excluded 315 further trials as too poor to use. In a 2013 comparison of fifteen antipsychotics it ranked as mildly effective, beating some newer drugs and trailing haloperidol and others.
Its range of other uses is surprisingly wide: stubborn hiccups, severe nausea, anxiety before surgery, and in Germany insomnia and severe itching. It has been tried as a trip killer to cut short the effects of LSD and psilocybin, with inconsistent results; intravenous doses reportedly abolish LSD's effects while oral doses are much weaker. Lab studies have found antimicrobial and anti-parasitic activity, and it strongly blocks certain insect receptors, including one in the silk moth.
Common side effects include sleepiness, dry mouth, weight gain, dizziness on standing and movement problems. Serious risks include tardive dyskinesia, neuroleptic malignant syndrome and a lowered seizure threshold, and in older people with dementia-related psychosis it may raise the risk of death. Controversially, some psychiatric patients have been given it by force.
Source: Chlorpromazine
