Tiapride

Last updated
Tiapride
Tiapride.svg
Clinical data
Trade names Tiapridal
Routes of
administration
Oral (tablets), IM, IV
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability ~75% (oral) (Tmax = 1 hour)
Protein binding Negligible
Elimination half-life 2.9–3.6 hours
Excretion Urine (70% as unchanged tiapride)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.051.717 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H24N2O4S
Molar mass 328.43 g·mol−1
3D model (JSmol)
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Tiapride is a drug that selectively blocks D2 and D3 dopamine receptors in the brain. It is used to treat a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly. [1] A derivative of benzamide, tiapride is chemically and functionally similar to other benzamide antipsychotics such as sulpiride and amisulpride known for their dopamine antagonist effects.

Contents

Medical uses

Alcoholism

Research in animal models and clinical studies in alcoholic patients have found that tiapride has anxiolytic effects. Dopamine hyperactivity has been linked with alcohol withdrawal syndrome (AWS), suggesting that tiapride's antidopaminergic effects are the most likely mechanism for its clinical efficacy, [2] although others believe some other mechanism might be involved. [3] Alcoholic patients treated with tiapride at a dosage of 300 mg/day reported reduced psychological distress and improved abstinence from alcohol. [3] In another study in which alcoholic patients were given titrated doses up to 800 mg/day, subjects showed significant improvements in ratings of withdrawal, craving, psychiatric symptoms and quality of life. [2]

While tiapride does not affect positive symptoms of psychosis such as hallucinosis or delirium sometimes manifested in alcohol withdrawal syndrome, if combined with a drug such as carbamazepine that addresses those symptoms, it is ideal for treating alcohol dependency because its metabolism does not depend on liver function and it has low potential for abuse. [2] This sets it apart from the benzodiazepines, which are contraindicated with alcohol and can be addictive. [3] Moreover, tiapride's rapid onset makes intravenous or intramuscular injection prior to or during withdrawal episodes particularly effective. [2]

Agitation and aggression

Agitation and aggression are also associated with hyperdopaminergic activity. Antipsychotic drugs are the most common treatment for these symptoms, but often come with a host of side-effects including orthostatic hypotension and deficits in vigilance and attention. One clinical study in agitated elderly patients compared the effects of tiapride, haloperidol and placebo and found that while the two drugs had comparable efficacy superior to the placebo effect, tiapride had fewer and less severe side effects than haloperidol. [4]

Tiapride's selectivity for the limbic system, which is associated with emotion, could underlie its particular efficacy in treating these affective disorders. Moreover, its selectivity for the dopaminergic system is thought to account for its avoidance of the side effects typically associated with other neuroleptic drugs, such as chlorpromazine, which act on a number of neurotransmitter systems. [1]

Movement disorders

While tiapride preferentially targets the limbic system over the striatum, its moderate antagonistic effect on striatal dopamine receptors makes it effective in treating motor deficits that involve this area, such as tardive dyskinesia and chorea. Tiapride's moderate efficacy at D2 receptors [5] may explain why it is able to treat motor symptoms without the extrapyramidal symptoms caused by excess dopamine blockage, which are sometimes seen in haloperidol or chlorpromazine. One clinical study of patients with tardive dyskinesia associated with Parkinson's disease found that tiapride significantly improved motor abilities without affecting other parkinsonian symptoms. [6]

Side effects

Although it is considered a "safe" medicine, it is, like sulpiride, strictly contraindicated for patients under the age of 18 due to its effects during the process of puberty. This is likely related to its side effects on levels of the hormone prolactin, which is involved in sexual development. [7] There are also insufficient clinical data on the other side effects in adolescents.

Tiapride has been found to cause excess prolactin levels in plasma, [6] which can cause decreased libido, infertility and increased risk of breast cancer. [8] This is because dopamine plays a primary role in regulating prolactin release by binding to D2 receptors on prolactin-secreting cells in the anterior pituitary. [9] Thus, when tiapride blocks these receptors these cells are disinhibited and release more prolactin.

The side-effect reported most commonly to the U.S. Food and Drug Administration (FDA) is rhabdomyolysis, a condition characterized by muscle tissue breakdown. [10] Cardiac abnormalities such as prolongation of the QT interval and torsades de pointes have also been observed. [8]

Dosages above approximately 300 mg/day risk inducing tardive dyskinesia. [3] However, given the drug's fairly wide window of tolerable doses, [1] dosages can often be titrated to obtain the desired effect without bringing about motor deficits. In general, tiapride is considered an atypical antipsychotic because of its low risk for extrapyramidal symptoms, such as akinesia and akathesia. These effects are thought to be reduced in tiapride relative to typical antipsychotics because of its selectivity for the limbic system over extrapyramidal areas that control movement. [1]

Pharmacodynamics

Tiapride is a dopamine D2 and D3 receptor antagonist. It is more selective than other neuroleptic drugs such as haloperidol and risperidone, which not only target four of the five known dopamine receptor subtypes (D1-4), but also block serotonin (5-HT2A, 2C), α1- and α2-adrenergic, and histamine H1 receptors. [1] Compared to these drugs, tiapride has a relatively moderate affinity for its target receptors, displacing 50 percent of 3H-raclopride binding at a concentration of 320 nM at D2 receptors and a concentration of 180 nM at D3 receptors.

Tiapride displays a relatively high regional selectivity for limbic areas. One study found that, in contrast with haloperidol, which displays equal affinity for receptors in the rat limbic system and striatum, tiapride shows over three times as much affinity for limbic areas than striatal areas. [1] Another study in rats found tiapride's affinity for the septum, a limbic region, to be over thirty times as high as for the striatum. [11]

Efficacy at the D2 receptor is moderate, with 80 percent of receptors occupied even in the presence of excess tiapride concentrations. [5]

Pharmacokinetics

Tiapride is primarily taken orally in the form of a tablet, but can also be administered via intravenous or intramuscular injection. [3] A liquid oral formulation is also available for elderly patients with difficulty chewing solids. [12] For all three methods of administration, the bioavailability of tiapride is approximately 75 percent. Peak plasma concentrations are attained between 0.4 and 1.5 hours following administration, and steady-state concentrations achieved 24 to 48 hours after beginning administration 3 times a day. It distributes rapidly and exhibits virtually no binding to plasma proteins, giving it a relatively high volume of distribution. Benzamide and its derivatives are highly water-soluble, and because of their polarity are believed to cross the blood–brain barrier via carrier-mediated transport. [13] Elimination of tiapride, mostly in its original form, occurs through renal excretion with a half-life of 3 to 4 hours. [3]

Recommended dosages of tiapride vary with clinical symptoms. In alcoholic patients, delirium or pre-delirium associated with alcohol withdrawal can be alleviated by administration of 400–1200 mg/day or up to 1800 mg/day if necessary. Tremors and other dyskinsias can be treated with 300–800 mg/day. For reducing agitation and aggression in elderly patients, 200–300 mg/day is recommended. [3]

Availability

Tiapride is marketed under various trade names and is widely available outside of the United States. The most common trade name for tiapride is Tiapridal, which is used throughout Europe, Russia, as well as parts of South America, the Middle East, and North Africa. It is also sold under different names in Italy (Italprid, Sereprile), Japan (Tialaread, Tiaryl, Tiaprim, Tiaprizal), Chile (Sereprid), Germany (Tiaprid, Tiapridex), and China (Tiapride). [14]

See also

Related Research Articles

Antipsychotic Class of medications

Antipsychotics, also known as neuroleptics, are a class of medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay together with mood stabilizers in the treatment of bipolar disorder.

Chlorpromazine Chemical compound

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, severe behavioral problems in children including those with 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.

Haloperidol Typical antipsychotic medication

Haloperidol, marketed under the trade name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, nausea and vomiting, delirium, agitation, acute psychosis, and hallucinations in alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks in people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

Typical antipsychotic class of pharmaceutical drugs

Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis. 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 larger supplanted the use of typical antipsychotics as first-line agents due to the higher risk of movement disorders in the latter.

Atypical antipsychotic Class of pharmaceutical drugs

The atypical antipsychotics are a group of antipsychotic drugs largely introduced after the 1970s and used to treat psychiatric conditions. Some atypical antipsychotics have received regulatory approval for schizophrenia, bipolar disorder, autism, and as an adjunct in major depressive disorder.

Olanzapine Medication

Olanzapine, sold under the trade name Zyprexa among others, is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new onset disease and long-term maintenance. It is taken by mouth or by injection into a muscle.

Pimozide chemical compound

Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine. 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.

Perphenazine chemical compound

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.

Tardive dyskinesia Neurological disorder following long-term dopamine antagonist use

Tardive dyskinesia (TD) is a disorder that results in involuntary, repetitive body movements, which may include grimacing, sticking out the tongue, or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movements. In about 20% of people, the disorder interferes with daily functioning.

Dopamine antagonist Drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therap

A dopamine antagonist (anti-dopaminergic) is a type of drug which blocks dopamine receptors by receptor antagonism. Most antipsychotics are dopamine antagonists, and as such they have found use in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

Progabide pharmaceutical drug

Progabide is an analogue and prodrug of γ-aminobutyric acid (GABA) used in the treatment of epilepsy. Via conversion into GABA, progabide behaves as an agonist of the GABAA, GABAB, and GABAA-ρ receptors.

Amisulpride Chemical compound

Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses orally and intramuscularly to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. It is also used to treat dysthymia.

Sulpiride Atypical antipsychotic

Sulpiride, sold under the brand name Dogmatil among others, is an atypical antipsychotic medication of the benzamide class which is used mainly in the treatment of psychosis associated with schizophrenia and major depressive disorder, and sometimes used in low dosage to treat anxiety and mild depression. Sulpiride is commonly used in Asia, Central America, Europe, South Africa and South America. Levosulpiride is its purified levo-isomer and is sold in India for similar purpose. It is not approved in the United States, Canada, or Australia. The drug is chemically and clinically similar to amisulpride.

Extrapyramidal symptoms (EPS), also known as extrapyramidal side effects (EPSE) if drug-induced, are movement disorders, which include acute and long term symptoms. These symptoms include dystonia, akathisia, parkinsonism, bradykinesia, tremor, and tardive dyskinesia. Extrapyramidal symptoms are a reason why subjects drop out of clinical trials of antipsychotics; of the 213 (14.6%) subjects that dropped out of the one of the largest clinical trials of antipsychotics, 58 (27.2%) of those discontinuations were due to EPS.

Asenapine An atypical antipsychotic medication used to treat schizophrenia

Asenapine, sold under the trade names Saphris and Sycrest among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder.

Zuclopenthixol chemical compound

Zuclopenthixol, also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol. Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.

Perospirone chemical compound

Perospirone (Lullan) is an atypical antipsychotic of the azapirone family. It was introduced in Japan by Dainippon Sumitomo Pharma in 2001 for the treatment of schizophrenia and acute cases of bipolar mania.

Levosulpiride Chemical compound

Levosulpiride, sold under the brand name Neoprad is a substituted benzamide antipsychotic, reported to be a selective antagonist of dopamine D2 receptor activity on both central and peripheral levels. It is an atypical neuroleptic and a prokinetic agent. Levosulpiride is also claimed to have mood elevating properties.

Piquindone chemical compound

Piquindone (Ro 22-1319) is an atypical antipsychotic with a tricyclic structure that was developed in the 1980s but was never marketed. It acts as a selective D2 receptor antagonist, though based on its effects profile its selectivity may be considered controversial. Unlike most other D2 receptor ligands, piquindone displays Na+-dependent binding, a property it shares with tropapride, zetidoline, and metoclopramide.

Aripiprazole lauroxil chemical compound

Aripiprazole lauroxil is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. FDA on 5 October 2015.

References

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