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Trade names | Serdolect, Serlect |
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Routes of administration | By mouth |
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Pharmacokinetic data | |
Bioavailability | 75% [1] |
Protein binding | 99.5% [1] |
Metabolism | Liver (mostly via CYP2D6 and CYP3A4) [2] [3] |
Elimination half-life | 3 days [2] |
Excretion | Faecal (the majority), Kidney (4% metabolites; 1% unchanged) [2] |
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ECHA InfoCard | 100.162.562 |
Chemical and physical data | |
Formula | C24H26ClFN4O |
Molar mass | 440.95 g·mol−1 |
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Sertindole, sold under the brand name Serdolect among others, is an antipsychotic medication. Sertindole was developed by the Danish pharmaceutical company Lundbeck and marketed under license by Abbott Labs. Like other atypical antipsychotics, it has activity at dopamine and serotonin receptors in the brain. It is used in the treatment of schizophrenia. It is classified chemically as a phenylindole derivative.
Sertindole is not approved for use in the United States and was discontinued in Australia in January 2014.[ citation needed ]
Sertindole appears effective as an antipsychotic in schizophrenia. [4] In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, sertindole was found to be slightly less effective than haloperidol, quetiapine, and aripiprazole, as effective as ziprasidone, approximately as effective as chlorpromazine and asenapine, and slightly more effective than lurasidone and iloperidone. [5]
Very common (>10% incidence) adverse effects include: [2]
Common (1–10% incidence) adverse effects include: [2]
Uncommon (0.1–1% incidence) adverse effects include: [2]
Rare (<0.1% incidence) adverse effects include: [2]
Unknown frequency adverse events include: [2]
Biologic protein | Binding affinity (Ki[nM]) [7] | Notes |
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5-HT1A | 280 | |
5-HT1B | 60 | |
5-HT1D | 96 | |
5-HT1E | 430 | |
5-HT1F | 360 | |
5-HT2A | 0.39 | The receptor believed to mediate the atypicality of atypical antipsychotics. [8] |
5-HT2C | 0.9 | Likely responsible for its propensity for causing weight gain. [8] |
5-HT6 | 5.4 | |
5-HT7 | 28 | |
α1A | 1.8 | Likely responsible for the orthostatic hypotension seen in patients on sertindole. [8] |
α2A | 640 | |
α2B | 450 | |
α2C | 450 | |
β1 | 5000 | |
β2 | 5000 | |
M1 | >10000 | [8] |
M3 | 2692 | |
D2 | 2.35 | Believed to be responsible for the drug's efficacy against positive symptoms. [8] |
D3 | 2.30 | |
D4 | 4.92 | |
hERG | 3 | Responsible for the QT interval prolongation and torsade de pointes |
H1 | 130 | |
NK1 | 1000 |
Sertindole is metabolized in the body to dehydrosertindole. [9]
Abbott Labs first applied for U.S. Food and Drug Administration (FDA) approval for sertindole in 1996, [10] but withdrew this application in 1998 following concerns over the increased risk of sudden death from QTc prolongation. [11] In a trial of 2000 patients on taking sertindole, 27 patients died unexpectedly, including 13 sudden deaths. [12] Lundbeck cites the results of the Sertindole Cohort Prospective (SCoP) study of 10,000 patients to support its claim that although sertindole does increase the QTc interval, this is not associated with increased rates of cardiac arrhythmias, and that patients on sertindole had the same overall mortality rate as those on risperidone. [13] Nevertheless, in April 2009 an FDA advisory panel voted 13-0 that sertindole was effective in the treatment of schizophrenia but 12-1 that it had not been shown to be acceptably safe. [14] As of October 2010 [update] , the drug has not been approved by the FDA for use in the USA. [15] [ failed verification ]
In the European Union, sertindole was approved and marketed in 19 countries from 1996, [12] but its marketing authorization was suspended by the European Medicines Agency in 1998 [16] and the drug was withdrawn from the market. In 2002, based on new data, the EMA's CHMP suggested that Sertindole could be reintroduced for restricted use in clinical trials, with strong safeguards including extensive contraindications and warnings for patients at risk of cardiac dysrhythmias, a recommended reduction in maximum dose from 24 mg to 20 mg in all but exceptional cases, and extensive ECG monitoring requirement before and during treatment. [17] [18] As of September 2020 [update] , sertindole is authorized in several states of the European Union. [19]
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic 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. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.
Haloperidol, sold under the brand 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, delirium, agitation, acute psychosis, and hallucinations from 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 by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), 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, irritability in autism, and as an adjunct in major depressive disorder.
Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder, as well as irritability associated with autism. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.
Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its sedating effect, the benefits of such use may not outweigh its undesirable side effects. It is taken orally.
Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation in people with schizophrenia.
Olanzapine, sold under the brand 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.
Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder; other uses include as an add-on treatment in major depressive disorder and obsessive–compulsive disorder (OCD), tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.
Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group.
Amisulpride is an antiemetic and antipsychotic medication used at lower doses intravenously to prevent and treat postoperative nausea and vomiting; and at higher doses by mouth to treat schizophrenia and acute psychotic episodes. It is sold under the brand names Barhemsys and Solian, Socian, Deniban and others. At very low doses it is also used to treat dysthymia.
Flupentixol (INN), also known as flupenthixol, marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug preparations, it is also available as flupentixol/melitracen—a combination product containing both melitracen and flupentixol . Flupentixol is not approved for use in the United States. It is, however, approved for use in the UK, Australia, Canada, Russian Federation, South Africa, New Zealand, Philippines, Iran, Germany, and various other countries.
Zotepine is an atypical antipsychotic drug indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 and Japan since 1982.
Asenapine, sold under the brand name Saphris among others, is an atypical antipsychotic medication used to treat schizophrenia and acute mania associated with bipolar disorder as well as the medium to long-term management of bipolar disorder.
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.
Lurasidone, sold under the brand name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.
Cariprazine, sold under the brand name Vraylar among others, is an atypical antipsychotic developed by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, bipolar depression, and major depressive disorder. It acts primarily as a D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors, with high selectivity for the D3 receptor. It is taken by mouth.
Brexpiprazole, sold under the brand name Rexulti among others, is an atypical antipsychotic medication used for the treatment of major depressive disorder, schizophrenia, and agitation associated with dementia due to Alzheimer's disease.
Antipsychotic abuse refers to the non-medical or inappropriate use of antipsychotic medications for purposes other than their intended therapeutic use. Antipsychotics, also known as neuroleptics, are a class of medications primarily used in treating psychiatric disorders such as schizophrenia, bipolar disorder, and certain types of depression. The misuse and abuse (MUA) of pharmaceuticals are typically linked to medications that elicit euphoria or other desirable effects, such as relaxation or increased alertness. Consequently, antipsychotics are not commonly categorized as significant substances prone to abuse. However, antipsychotics abuse may be attributed to its calming and sedative effects, and they have been exploited to either enhance the effects of illicit substances like cocaine and marijuana or counteract their adverse consequences. Due to the potential of physical, social, and psychological consequences in patients using antipsychotics, the prevention and protection of these patient populations from the MUA of drugs has been implemented via various legislations worldwide which differ depending on the local jurisdiction.