Clinical data | |
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Trade names | Zoleptil |
AHFS/Drugs.com | International Drug Names |
Routes of administration | Oral |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | 7–13% (oral) [2] |
Metabolism | N-desmethylation to norzotepine (30-40%) [2] |
Elimination half-life | 13.7–15.9 hours, 12 hours (Norzotepine) [2] |
Excretion | 17% (Urine) [2] |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.189.143 |
Chemical and physical data | |
Formula | C18H18ClNOS |
Molar mass | 331.86 g·mol−1 |
3D model (JSmol) | |
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Zotepine is an atypical antipsychotic drug indicated for acute and chronic schizophrenia. It has been used in Germany since 1990 (although it has been discontinued in Germany) and Japan since 1982.
Zotepine is not approved for use in the United States, United Kingdom, Australia, Canada or New Zealand. [3]
Zotepine's primary use is as a treatment for schizophrenia [4] although clinical trials have been conducted (with positive results) into its efficacy as an antimanic agent in patients with acute bipolar mania. [5] [6] [7] In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, zotepine demonstrated medium-strong effectivity. Less effective than clozapine, slightly less effective than olanzapine and risperidone, approximately as effective as paliperidone, and slightly more effective than haloperidol, quetiapine, and aripiprazole. [8]
The antipsychotic effect of zotepine is thought to be mediated through antagonist activity at dopamine and serotonin receptors. Zotepine has a high affinity for the D1 and D2 receptors. It also affects the 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors. [10] In addition, its active metabolite, norzotepine, serves as a potent norepinephrine reuptake inhibitor. [11]
Macromolecule (Receptor or transporter protein) | Ki [nM] [10] |
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SERT | 151 |
NET | 530 |
DAT | 3621 |
5-HT1A | 470.5 |
5-HT1B | 59.5 |
5-HT1D | 119 |
5-HT1E | 700 |
5-HT2A | 2.7 |
5-HT2C | 2.6 |
5-HT3 | 472 |
5-HT5A | 29 |
5-HT6 | 6 |
5-HT7 | 12 |
α1A | 7 |
α1B | 5 |
α2A | 180 |
α2B | 5.35 |
α2C | 106 |
M1 | 18 |
M2 | 140 |
M3 | 73 |
M4 | 77 |
M5 | 260 |
D1 | 71 |
D2 | 25 |
D2S | 5.4 |
D2L | 11 |
D3 | 6.4 |
D4 | 18 |
D5 | 248 |
H1 | 3.21 |
H2 | 500 |
H4 | 1977 |
Brand names include Losizopilon(JP), Lodopin(ID, JP), Setous(JP), Zoleptil(CZ, PT, TR, UK†); where † indicates a formulation that has been discontinued.
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.
Clozapine is the first atypical antipsychotic medication to have been discovered. It is usually used in tablet or liquid form for people diagnosed with schizophrenia who have had an inadequate response to other antipsychotics or who have been unable to tolerate other drugs due to extrapyramidal side effects. It is also used for the treatment of psychosis in Parkinson's disease. In the US it is also licensed for use in patients with recurrent suicidal behaviour associated with schizophrenia or schizoaffective disorder. It is regarded as the gold-standard treatment when other medication has been insufficiently effective and its use is recommended by multiple international treatment guidelines. Compared to other antipsychotic drug treatments, initiating and maintaining clozapine is complex, expensive and time-consuming. The role of clozapine in treatment-resistant schizophrenia was established by the Clozaril Collaborative Study Group Study #30 in which clozapine showed marked benefits compared to chlorpromazine in a group of patients with protracted psychosis and who had already shown an inadequate response to other antipsychotics. There are a range of different adverse effects and compulsory blood monitoring is required in most developed countries. Whilst there are significant side effects, clozapine remains the most effective treatment when one or more other antipsychotics have had an inadequate response, and clozapine use is associated with multiple improved outcomes including all cause mortality, suicide and reduced hospitalisation. In a network comparative meta-analysis of 15 antipsychotic drugs, clozapine was significantly more effective than all other drugs. Surveys of patient satisfaction show preference over other antipsychotics.
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. 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 do not appear to generally outweigh the 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 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, obsessive compulsive disorder (OCD), and bipolar disorder; other uses include as an add-on treatment in major depressive disorder, 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.
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.
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.
Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder. It is marketed by Janssen Pharmaceuticals. Paliperidone was approved by the FDA for the treatment of schizophrenia on December 20, 2006. Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester.
Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side effects (EPSE). The symptoms can be acute (short-term) or chronic (long-term). They include movement dysfunction such as dystonia, akathisia, parkinsonism characteristic symptoms such as rigidity, 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 one of the largest clinical trials of antipsychotics, 58 (27.2%) of those discontinuations were due to EPS.
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.
Iloperidone, commonly known as Fanapt and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia.
Lurasidone, sold under the trade name Latuda among others, is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is taken by mouth.