Chlorpromazine (CPZ), marketed under the trade names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given by mouth, by injection into a muscle, or into a vein.
Common side effects include movement problems, sleepiness, dry mouth, low blood pressure upon standing, and increased weight. Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, neuroleptic malignant syndrome, and low white blood cell levels. In older people with psychosis as a result of dementia it may increase the risk of death. It is unclear if it is safe for use in pregnancy. Chlorpromazine is in the typical antipsychotic class. Its mechanism of action is not entirely clear but believed to be related to its ability as a dopamine antagonist. It also has anti-serotonergic and antihistaminergic properties.
Chlorpromazine was discovered in 1950 and was the first antipsychotic. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Its introduction has been labeled as one of the great advances in the history of psychiatry. It is available as a generic medication. The wholesale cost in the developing world is between US$0.02 and US$0.12 per day. In the United States the wholesale costs is about US$7.80 per day as of 2019.
|Trade names||Largactil, Thorazine, many others|
|Oral (tablets and syrup available), rectal, IM, IV infusion|
|Bioavailability||10–80% (Oral; large interindividual variation)|
|Metabolism||Liver, mostly CYP2D6-mediated|
|Elimination half-life||30 hours|
|Excretion||Urine (43–65% in 24 hrs)|
|Chemical and physical data|
|Molar mass||318.86 g/mol (free base)|
355.33 g/mol (hydrochloride) g·mol−1
|3D model (JSmol)|
Chlorpromazine is classified as a low-potency typical antipsychotic and in the past was used in the treatment of both acute and chronic psychoses, including schizophrenia and the manic phase of bipolar disorder, as well as amphetamine-induced psychosis. Low-potency antipsychotics have more anticholinergic side effects, such as dry mouth, sedation, and constipation, and lower rates of extrapyramidal side effects, while high-potency antipsychotics (such as haloperidol) have the reverse profile.
In a 2013 comparison of 15 antipsychotics in schizophrenia, chlorpromazine demonstrated mild-standard effectiveness. It was 13% more effective than lurasidone and iloperidone, approximately as effective as ziprasidone and asenapine, and 12-16% less effective than haloperidol, quetiapine, and aripiprazole.
Chlorpromazine has also been used in porphyria and as part of tetanus treatment. It still is recommended for short-term management of severe anxiety and psychotic aggression. Resistant and severe hiccups, severe nausea/emesis, and preanesthetic conditioning are other uses. Symptoms of delirium in hospitalized AIDS patients have been effectively treated with low doses of chlorpromazine.
Chlorpromazine is occasionally used off-label for treatment of severe migraine. It is often, particularly as palliation, used in small doses to reduce nausea suffered by opioid-treated cancer patients and to intensify and prolong the analgesia of the opioids as well.
|Measured outcome||Findings in words||Findings in numbers||Quality of evidence|
|Not any improvement (9 weeks – 6 months)||30% less risk of having no improvement in mental state, behaviour and functioning||RR 0.7 CI 0.6 to 0.9||Very low (estimate of effect uncertain)|
|Relapse (6 months – 2 years)||35% less risk of relapse||RR 0.7 CI 0.5 to 0.9|
There appears to be a dose-dependent risk for seizures with chlorpromazine treatment. Tardive dyskinesia (involuntary, repetitive body movements) and akathisia (a feeling of inner restlessness and inability to stay still) are less commonly seen with chlorpromazine than they are with high potency typical antipsychotics such as haloperidol or trifluoperazine, and some evidence suggests that, with conservative dosing, the incidence of such effects for chlorpromazine may be comparable to that of newer agents such as risperidone or olanzapine.
Chlorpromazine may deposit in ocular tissues when taken in high dosages for long periods of time.
|Measured outcome||Findings in words||Findings in numbers||Quality of evidence|
|Weight gain||5 times more likely to have considerable weight gain, around 40% with chlorpromazine gaining weight||RR 4.9 CI 2.3 to 10.4||Very low (estimate of effect uncertain)|
|Sedation||3 times more likely to cause sedation, around 30% with chlorpromazine||RR 2.8 CI 2.3 to 3.5|
|Acute movement disorder||3.5 times more likely to cause easily reversible but unpleasant severe stiffening of muscles, around 6% with chlorpromazine||RR 3.5 CI 1.5 to 8.0|
|Parkinsonism||2 times more likely to cause parkinsonism (symptoms such as tremor, hesitancy of movement, decreased facial expression), around 17% with chlorpromazine||RR 2.1 CI 1.6 to 2.8|
|Decreased blood pressure with dizziness||3 times more likely to cause decreased blood pressure and dizziness, around 15% with chlorpromazine||RR 2.4 CI 1.7 to 3.3|
Absolute contraindications include:
Relative contraindications include:
Very rarely, elongation of the QT interval may occur, increasing the risk of potentially fatal arrhythmias.
Consuming food prior to taking chlorpromazine orally limits its absorption, likewise cotreatment with benztropine can also reduce chlorpromazine absorption. Alcohol can also reduce chlorpromazine absorption. Antacids slow chlorpromazine absorption. Lithium and chronic treatment with barbiturates can increase chlorpromazine clearance significantly. Tricyclic antidepressants (TCAs) can decrease chlorpromazine clearance and hence increase chlorpromazine exposure. Cotreatment with CYP1A2 inhibitors like ciprofloxacin, fluvoxamine or vemurafenib can reduce chlorpromazine clearance and hence increase exposure and potentially also adverse effects. Chlorpromazine can also potentiate the CNS depressant effects of drugs like barbiturates, benzodiazepines, opioids, lithium and anesthetics and hence increase the potential for adverse effects such as respiratory depression and sedation.
It is also a moderate inhibitor of CYP2D6 and also a substrate for CYP2D6 and hence can inhibit its own metabolism. It can also inhibit the clearance of CYP2D6 substrates such as dextromethorphan and hence also potentiate their effects. Other drugs like codeine and tamoxifen which require CYP2D6-mediated activation into their respective active metabolites may have their therapeutic effects attenuated. Likewise CYP2D6 inhibitors such as paroxetine or fluoxetine can reduce chlorpromazine clearance and hence increase serum levels of chlorpromazine and hence potentially also its adverse effects. Chlorpromazine also reduces phenytoin levels and increases valproic acid levels. It also reduces propranolol clearance and antagonizes the therapeutic effects of antidiabetic agents, levodopa (a Parkinson's medication. This is likely due to the fact that chlorpromazine antagonizes the D2 receptor which is one of the receptors dopamine, a levodopa metabolite, activates), amphetamines and anticoagulants. It may also interact with anticholinergic drugs such as orphenadrine to produce hypoglycaemia (low blood sugar).
Chlorpromazine may also interact with epinephrine (adrenaline) to produce a paradoxical fall in blood pressure. Monoamine oxidase inhibitors (MAOIs) and thiazide diuretics may also accentuate the orthostatic hypotension experienced by those receiving chlorpromazine treatment. Quinidine may interact with chlorpromazine to increase myocardialdepression. Likewise it may also antagonize the effects of clonidine and guanethidine. It also may reduce the seizure threshold and hence a corresponding titration of anticonvulsant treatments should be considered. Prochlorperazine and desferrioxamine may also interact with chlorpromazine to produce transient metabolic encephalopathy.
The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse. While withdrawal symptoms can occur, there is no evidence that tolerance develops to the drug's antipsychotic effects. A person can be maintained for years on a therapeutically effective dose without any decrease in effectiveness being reported. Tolerance appears to develop to the sedating effects of chlorpromazine when it is first administered. Tolerance also appears to develop to the extrapyramidal, parkinsonian and other neuroleptic effects, although this is debatable.
A failure to notice withdrawal symptoms may be due to the relatively long half life of the drug resulting in the extremely slow excretion from the body. However, there are reports of muscular discomfort, exaggeration of psychotic symptoms and movement disorders, and difficulty sleeping when the antipsychotic drug is suddenly withdrawn, but after years of normal doses these effects are not normally seen.
|Bioavailability||tmax||CSS||Protein bound||Vd||t1/2||Details of metabolism||Excretion||Notes|
|10–80%||1–4 hours (Oral); 6–24 hours (IM)||100–300 ng/mL||90–99%||10–35 L/kg (mean: 22 L/kg)||30±7 hours||CYP2D6, CYP1A2—mediated into over 10 major metabolites. The major routes of metabolism include hydroxylation, N-oxidation, sulphoxidation, demethylation, deamination and conjugation. There is little evidence supporting the development of metabolic tolerance or an increase in the metabolism of chlorpromazine due to microsomal liver enzymes following multiple doses of the drug.||Urine (43–65% after 24 hours)||Its high degree of lipophilicity (fat solubility) allows it to be detected in the urine for up to 18 months. Less than 1% of the unchanged drug is excreted via the kidneys in the urine, in which 20–70% is excreted as conjugated or unconjugated metabolites, whereas 5–6% is excreted in feces.|
Chlorpromazine is a very effective antagonist of D2 dopamine receptors and similar receptors, such as D3 and D5. Unlike most other drugs of this genre, it also has a high affinity for D1 receptors. Blocking these receptors causes diminished neurotransmitter binding in the forebrain, resulting in many different effects. Dopamine, unable to bind with a receptor, causes a feedback loop that causes dopaminergic neurons to release more dopamine. Therefore, upon first taking the drug, patients will experience an increase in dopaminergic neural activity. Eventually, dopamine production of the neurons will drop substantially and dopamine will be removed from the synaptic cleft. At this point, neural activity decreases greatly; the continual blockade of receptors only compounds this effect.
Chlorpromazine acts as an antagonist (blocking agent) on different postsynaptic and presynaptic receptors:
The presumed effectiveness of the antipsychotic drugs relied on their ability to block dopamine receptors. This assumption arose from the dopamine hypothesis that maintains that both schizophrenia and bipolar disorder are a result of excessive dopamine activity. Furthermore, psychomotor stimulants like cocaine that increase dopamine levels can cause psychotic symptoms if taken in excess.
Chlorpromazine and other typical antipsychotics are primarily blockers of D2 receptors. In fact an almost perfect correlation exists between the therapeutic dose of a typical antipsychotic and the drug's affinity for the D2 receptor. Therefore, a larger dose is required if the drug’s affinity for the D2 receptor is relatively weak. A correlation exists between average clinical potency and affinity of the antipsychotics for dopamine receptors. Chlorpromazine tends to have greater effect at serotonin receptors than at D2 receptors, which is notably the opposite effect of the other typical antipsychotics. Therefore, chlorpromazine with respect to its effects on dopamine and serotonin receptors is more similar to the atypical antipsychotics than to the typical antipsychotics.
Chlorpromazine and other antipsychotics with sedative properties such as promazine and thioridazine are among the most potent agents at α-adrenergic receptors. Furthermore, they are also among the most potent antipsychotics at histamine H1 receptors. This finding is in agreement with the pharmaceutical development of chlorpromazine and other antipsychotics as anti-histamine agents. Furthermore, the brain has a higher density of histamine H1 receptors than any body organ examined which may account for why chlorpromazine and other phenothiazine antipsychotics are as potent at these sites as the most potent classical antihistamines.
In addition to influencing the neurotransmitters dopamine, serotonin, epinephrine, norepinephrine, and acetylcholine it has been reported that antipsychotic drugs could achieve glutamanergic effects. This mechanism involves direct effects on antipsychotic drugs on glutamate receptors. By using the technique of functional neurochemical assay chlorpromazine and phenothiazine derivatives have been shown to have inhibitory effects on NMDA receptors that appeared to be mediated by action at the Zn site. It was found that there is an increase of NMDA activity at low concentrations and suppression at high concentrations of the drug. No significant difference in glutamate and glycine activity from the effects of chlorpromazine were reported. Further work will be necessary to determine if the influence in NMDA receptors by antipsychotic drugs contributes to their effectiveness.
Chlorpromazine is an antagonist to H1 receptors (provoking antiallergic effects), H2 receptors (reduction of forming of gastric juice), M1 and M2 receptors (dry mouth, reduction in forming of gastric juice) and some 5-HT receptors (different anti-allergic/gastrointestinal actions).
In 1933, the French pharmaceutical company Laboratoires Rhône-Poulenc began to search for new anti-histamines. In 1947, it synthesized promethazine, a phenothiazine derivative, which was found to have more pronounced sedative and antihistaminic effects than earlier drugs. A year later, the French surgeon Pierre Huguenard used promethazine together with pethidine as part of a cocktail to induce relaxation and indifference in surgical patients. Another surgeon, Henri Laborit, believed the compound stabilized the central nervous system by causing "artificial hibernation", and described this state as "sedation without narcosis". He suggested to Rhône-Poulenc that they develop a compound with better stabilizing properties. In December 1950, the chemist Paul Charpentier produced a series of compounds that included RP4560 or chlorpromazine. Simone Courvoisier conducted behavioural tests and found chlorpromazine produced indifference to aversive stimuli in rats. Chlorpromazine was distributed for testing to physicians between April and August 1951. Laborit trialled the medicine on at the Val-de-Grâce military hospital in Paris, using it as an anaesthetic booster in intravenous doses of 50 to 100 mg on surgery patients and confirming it as the best drug to date in calming and reducing shock, with patients reporting improved well being afterwards. He also noted its hypothermic effect and suggested it may induce artificial hibernation. Laborit thought this would allow the body to better tolerate major surgery by reducing shock, a novel idea at the time. Known colloquially as "Laborit's drug", chlorpromazine was released onto the market in 1953 by Rhône-Poulenc and given the trade name Largactil, derived from large "broad" and acti* "activity.
Following on, Laborit considered whether chlorpromazine may have a role in managing patients with severe burns, Raynaud's phenomenon, or psychiatric disorders. At the Villejuif Mental Hospital in November 1951, he and Montassut administered an intravenous dose to psychiatrist Cornelia Quarti who was acting as a volunteer. Quarti noted the indifference, but fainted upon getting up to go to the toilet, and so further testing was discontinued (orthostatic hypotension is a possible side effect of chlorpromazine). Despite this, Laborit continued to push for testing in psychiatric patients during early 1952. Psychiatrists were reluctant initially, but on January 19, 1952, it was administered (alongside pethidine, pentothal and ECT) to Jacques Lh. a 24-year-old manic patient, who responded dramatically, and was discharged after three weeks having received 855 mg of the drug in total.
Pierre Deniker had heard about Laborit's work from his brother-in-law, who was a surgeon, and ordered chlorpromazine for a clinical trial at the Sainte-Anne Hospital Center in Paris where he was Men's Service Chief. Together with the Director of the hospital, Professor Jean Delay, they published their first clinical trial in 1952, in which they treated 38 psychotic patients with daily injections of chlorpromazine without the use of other sedating agents. The response was dramatic; treatment with chlorpromazine went beyond simple sedation with patients showing improvements in thinking and emotional behaviour. They also found that doses higher than those used by Laborit were required, giving patients 75–100 mg daily.
Deniker then visited America, where the publication of their work alerted the American psychiatric community that the new treatment might represent a real breakthrough. Heinz Lehmann of the Verdun Protestant Hospital in Montreal trialled it in 70 patients and also noted its striking effects, with patients' symptoms resolving after many years of unrelenting psychosis. By 1954, chlorpromazine was being used in the United States to treat schizophrenia, mania, psychomotor excitement, and other psychotic disorders. Rhône-Poulenc licensed chlorpromazine to Smith Kline & French (today's GlaxoSmithKline) in 1953. In 1955 it was approved in the United States for the treatment of emesis (vomiting). The effect of this drug in emptying psychiatric hospitals has been compared to that of penicillin and infectious diseases. But the popularity of the drug fell from the late 1960s as newer drugs came on the scene. From chlorpromazine a number of other similar antipsychotics were developed. It also led to the discovery of antidepressants.
Chlorpromazine largely replaced electroconvulsive therapy, hydrotherapy, psychosurgery, and insulin shock therapy. By 1964, about 50 million people worldwide had taken it. Chlorpromazine, in widespread use for 50 years, remains a "benchmark" drug in the treatment of schizophrenia, an effective drug although not a perfect one. The relative strengths or potencies of other antipsychotics are often ranked or measured against chlorpromazine in aliquots of 100 mg, termed chlorpromazine equivalents or CPZE.
Chlorpromazine may be used as an antiemetic in dogs and cats, or, less often, as sedative prior to anesthesia. In horses, it often causes ataxia and lethargy, and is therefore seldom used.
It is commonly used to decrease nausea in animals that are too young for other common anti-emetics. It is also sometimes used as a preanesthetic and muscle relaxant in cattle, swine, sheep, and goats.
When the patient lashes out against 'them' — THORAZINE (brand of chlorpromazine) quickly puts an end to his violent outburst. 'Thorazine' is especially effective when the psychotic episode is triggered by delusions or hallucinations. At the outset of treatment, Thorazine's combination of antipsychotic and sedative effects provides both emotional and physical calming. Assaultive or destructive behavior is rapidly controlled. As therapy continues, the initial sedative effect gradually disappears. But the antipsychotic effect continues, helping to dispel or modify delusions, hallucinations and confusion, while keeping the patient calm and approachable. SMITH KLINE AND FRENCH LABORATORIES leaders in psychopharmaceutical researchMissing or empty
Bifeprunox (INN) (code name DU-127,090) is an atypical antipsychotic which, similarly to aripiprazole, combines minimal D2 receptor agonism with serotonin receptor agonism. It was under development for the treatment of schizophrenia but has since been abandoned.Bifeprunox has a novel mechanism of action. Conventional antipsychotics are classed into typical and atypical. The typical antipsychotics, such as chlorpromazine and haloperidol, are potent D2 receptor antagonists. The atypical antipsychotics started with clozapine, these are classified as multireceptor interacting compounds, acting as an agonist towards 5-HT1A and an antagonist towards D2 receptors among other 5-HT and DA receptors. Bifeprunox and other novel atypical antipsychotics will instead of antagonizing D2 receptors, will act as partial agonists, as well as partial agonists towards 5-HT1A receptors.In a multi-center, placebo-controlled study, 20 mg of bifeprunox was found to be significantly more effective than placebo at reducing symptoms of schizophrenia, with a low incidence of side effects.An NDA for Bifeprunox was filed with the U.S. Food and Drug Administration in January 2007. The FDA rejected the application in August 2007. In June 2009, Solvay and Lundbeck decided to cease development because "efficacy data did not support pursuing the existing development strategy of stabilisation of non-acute patients with schizophrenia."Butaclamol
Butaclamol (AY-23,028) is a typical antipsychotic which was never marketed. Sold as the hydrochloride salt for use in research, the compound acts as a dopamine receptor antagonist.Clocapramine
Clocapramine (Clofekton, Padrasen), also known as 3-chlorocarpipramine, is an atypical antipsychotic of the imidobenzyl class which was introduced in Japan in 1974 by Yoshitomi for the treatment of schizophrenia. In addition to psychosis, clocapramine has also been used to augment antidepressants in the treatment of anxiety and panic.Clocapramine has been reported to act as an antagonist of the D2, 5-HT2A, α1-adrenergic, and α2-adrenergic receptors, and does not inhibit the reuptake of either serotonin or norepinephrine. It has also been shown to have affinity for the σ receptors. Clocapramine's affinity for the 5-HT2A receptor is greater than that for the D2 receptor and it has a lower propensity for inducing extrapyramidal symptoms compared to typical antipsychotics, thus underlying its atypical nature.In several clinical trials, clocapramine has been compared to other neuroleptic agents. Against haloperidol, though there was no significant difference in efficacy at the end of the study, clocapramine tended to be superior in alleviating motor retardation, alogia, and thought disorder, and also produced fewer side effects. Against sulpiride, clocapramine demonstrated more favorable effects in the treatment of both positive and negative symptoms, including motor retardation, delusions, hallucinations, and social isolation, though it produced more side effects. Against timiperone, clocapramine showed lower efficacy against both positive and negative symptoms and produced more side effects such as dyskinesia, insomnia, constipation, and nausea.Clocapramine has been implicated in at least one fatality, a suicide in which there were two self-inflicted stab wounds and an overdose of clocapramine as well as three other antipsychotics was taken. The stab wounds could not explain the death, and thus, it was attributed to multiple drug toxicity instead.Fluphenazine
Fluphenazine, sold under the brand names Prolixin among others, is an antipsychotic medication. It is used in the treatment of chronic psychoses such as schizophrenia, and appears to be about equal in effectiveness to low-potency antipsychotics like chlorpromazine. It is given by mouth, injection into a muscle, or just under the skin. There is also a long acting injectable version that may last for up to four weeks. Fluphenazine decanoate, the depot injection form of fluphenazine, should not be used by people with severe depression.Common side effects include movement problems, sleepiness, depression and increased weight. Serious side effects may include neuroleptic malignant syndrome, low white blood cell levels, and the potentially permanent movement disorder tardive dyskinesia. In older people with psychosis as a result of dementia it may increase the risk of dying. It may also increase prolactin levels which may result in milk production, enlarged breasts in males, impotence, and the absence of menstrual periods. It is unclear if it is safe for use in pregnancy. Fluphenazine is a typical antipsychotic of the phenothiazine class. Its mechanism of action is not entirely clear but believed to be related to its ability to block dopamine receptors. In up to 40% of those on long term phenothiazines, liver function tests become mildly abnormal.Fluphenazine came into use in 1959. The injectable form is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. It is available as a generic medication. In the United States the tablets costs between 0.22 and 0.42 USD per day for a typical dose. The wholesale cost in the developing world of the long acting form is between 0.20 and 6.20 USD per injection as of 2014. It was discontinued in Australia around mid 2017.Gevotroline
Gevotroline (WY-47,384) is an atypical antipsychotic with a tricyclic structure which was under development for the treatment of schizophrenia by Wyeth-Ayerst. It acts as a balanced, modest affinity D2 and 5-HT2 receptor antagonist and also possesses high affinity for the sigma receptor. It was well-tolerated and showed efficacy in phase II clinical trials but was never marketed.Mosapramine
Mosapramine (Cremin) is an atypical antipsychotic used in Japan. It is a potent dopamine antagonist with high affinity to the D2, D3, and D4 receptors, and with moderate affinity for the 5-HT2 receptors.Ocaperidone
Ocaperidone (also R 79598) is a benzisoxazole antipsychotic. It was initially developed by Janssen, later licensed to French laboratory Neuro3D and then acquired in 2007 by German company Evotec. Its testing was abandoned after phase II trials, as of 22 February 2010.Perlapine
Perlapine, sold under the brand names Hypnodine and Pipnodine, is a hypnotic and sedative of the tricyclic group which is marketed in Japan. It acts primarily as a potent antihistamine, and also has anticholinergic, antiserotonergic, antiadrenergic, and some antidopaminergic activity. The drug has relatively weak affinity for the dopamine D2 receptor (IC50 = 1,803 nM) and, in accordance, is said to be ineffective as an antipsychotic. However, it retains higher affinity for the dopamine D1 receptor (IC50 = 198 nM). Its IC50 values are 19 nM for the α1-adrenergic receptor, 4,945 nM for the α2-adrenergic recpetor, and 70 nM for the serotonin 5-HT2A receptor. Perlapine is closely related to clotiapine, clozapine, fluperlapine, loxapine, and tilozepine.Perphenazine
Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the US as Trilafon, it has been in clinical use for decades.
Perphenazine is roughly five times as potent as chlorpromazine; thus perphenazine is considered a medium-potency antipsychotic.Phenothiazine
Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. The derivative chlorpromazine revolutionized the field of psychiatry and allergy treatment. An earlier derivative, methylene blue, was one of the first antimalarial drugs, and derivatives are under investigation as possible anti-infective drugs. Phenothiazine is a prototypical pharmaceutical lead structure in medicinal chemistry.Pimozide
Pimozide (sold under the brand name Orap) is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis it is even more potent than haloperidol. It also has special neurologic indications for Tourette syndrome and resistant tics. The side effects include akathisia, tardive dyskinesia, and, more rarely, neuroleptic malignant syndrome and prolongation of the QT interval.Prochlorperazine
Prochlorperazine is a dopamine (D2) receptor antagonist that belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It is also a highly potent typical antipsychotic, 10–20 times more potent than chlorpromazine. It is also used to treat migraine headaches. Intravenous administration can be used to treat status migrainosus.Promethazine
Promethazine is a first-generation antihistamine. It is used to treat allergies, trouble sleeping, and nausea. It may help with some symptoms associated with the common cold. It may also be used for sedating people who are agitated or anxious. It is available by mouth as a syrup, as a rectal suppository, or by injection into a muscle.Common side effects include confusion and sleepiness and sedation. Alcohol or other sedatives can make this worse. It is unclear if use during pregnancy or breastfeeding is safe for the baby. Use is not recommended in those less than two years old due to potentially negative effects on breathing. Use by injection into a vein is not recommended due to potential skin damage. It 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. The wholesale cost of the by mouth formulation is less than US$0.20 per dose as of 2018. In the United Kingdom this dose costs less than 0.25 pounds.Spiperone
Spiperone (Spiroperidol; brand name: Spiropitan (JP)) is a typical antipsychotic and research chemical belonging to the butyrophenone chemical class. It is licensed for clinical use in Japan as a treatment for schizophrenia. Additionally, spiperone was identified by compound screening to be an activator of Ca2+ activated Cl− channels (CaCCs), thus a potential target for therapy of cystic fibrosis.
N-Methylspiperone (NMSP) is a derivate of spiperone that is used to study the dopamine and serotonin neurotransmitter system.
Labeled with the radioisotope carbon-11, it can be used for positron emission tomography.Tetracyclic antidepressant
Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their tetracyclic chemical structure, containing four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.Tiotixene
Tiotixene, or thiothixene, sold under the brand name Navane among others, is a typical antipsychotic of the thioxanthene class which is related to chlorprothixene and is used in the treatment of psychoses like schizophrenia and bipolar mania. It was introduced in the United States in 1967 by Pfizer.Trifluoperazine
Trifluoperazine, sold under a number of brand names, is a typical antipsychotic primarily used to treat schizophrenia. It may also be used short term in those with generalized anxiety disorder but is less preferred to benzodiazepines. It is of the phenothiazine chemical class.Typical antipsychotic
Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to come into medical use were the phenothiazines, namely chlorpromazine which was discovered serendipitously. Another prominent grouping of antipsychotics are the butyrophenones, an example of which would be haloperidol. The newer, second-generation antipsychotics, also known as atypical antipsychotics, have replaced the typical antipsychotics due to the Parkinson-like side effects typicals have.
Both generations of medication tend to block receptors in the brain's dopamine pathways, but atypicals at the time of marketing were claimed to differ from typical antipsychotics in that they are less likely to cause extrapyramidal motor control disabilities in patients, which include unsteady Parkinson's disease-type movements, body rigidity and involuntary tremors. More recent research has demonstrated the side effect profile of these drugs is similar to older drugs, causing the leading medical journal The Lancet to write in its editorial "the time has come to abandon the terms first-generation and second-generation antipsychotics, as they do not merit this distinction." These abnormal body movements can become permanent even after medication is stopped. While typical antipsychotics are more likely to cause parkinsonism, atypicals are more likely to cause weight gain and type II diabetes.