Chlorpromazine (CPZ), marketed under the brand 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 orally, by intramuscular injection, or intravenously.
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.
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.
Loxapine, sold under the brand names Loxitane and Adasuve among others, is a tricyclic antipsychotic medication used primarily in the treatment of schizophrenia. The medicine is a member of the dibenzoxazepine class and structurally very similar to clozapine. Several researchers have argued that loxapine, initially classified as a typical antipsychotic, behaves as an atypical antipsychotic.
The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model that attributes the positive symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have dopamine-receptor antagonistic effects. The theory, however, does not posit dopamine overabundance as a complete explanation for schizophrenia. Rather, the overactivation of D2 receptors, specifically, is one effect of the global chemical synaptic dysregulation observed in this disorder.
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through different protein interactions. The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.
Dopaminergic means "related to dopamine", a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.
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.
A dopamine agonist is a compound that activates dopamine receptors. There are two families of dopamine receptors, D1-like and D2-like. They are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of the motor symptoms of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. Impulse control disorders are associated with the use of dopamine agonists for whatever condition.
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.
Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2 gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, including those of Solomon H. Snyder and Philip Seeman used a radiolabeled antipsychotic drug to identify what is now known as the dopamine D2 receptor. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 in complex with the atypical antipsychotic risperidone has been determined.
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family — receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.
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.
Blonanserin, sold under the brand name Lonasen, is a relatively new atypical antipsychotic commercialized by Dainippon Sumitomo Pharma in Japan and Korea for the treatment of schizophrenia. Relative to many other antipsychotics, blonanserin has an improved tolerability profile, lacking side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As with many second-generation (atypical) antipsychotics it is significantly more efficacious in the treatment of the negative symptoms of schizophrenia compared to first-generation (typical) antipsychotics such as haloperidol.
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.
F-15,063 is an orally active potential antipsychotic, and an antagonist at the D2/D3 receptors, partial agonist at the D4 receptor, and agonist at the 5-HT1A receptors. It has greater efficacy at the 5-HT1A receptors than other antipsychotics, such as clozapine, aripiprazole, and ziprasidone. This greater efficacy may lead to enhanced antipsychotic properties, as antipsychotics that lack 5-HT1A affinity are associated with increased risk of extrapyramidal symptoms, and lack of activity against the negative symptoms of schizophrenia.
The dopamine hypothesis of stuttering attributes to the phenomenon of stuttering a hyperactive and disturbed dopaminergic signal transduction in the brain. The theory is derived from observations in medical neuroimaging and from the empirical response of some antipsychotics and their antagonistic effects on the dopamine receptor. However, it is important to outline that the hypothesis does not consider the excessive dopaminergic activity as the direct cause of stuttering; instead, this synaptic dysregulation is a symptom of a greater disorder that affects other brain pathways and structures.
ENX-104 is a selective dopamine D2 and D3 receptor antagonist which is under development for the treatment of major depressive disorder. It is specifically under development for the treatment of major depressive disorder characterized by anhedonia. The drug is being developed for use at low doses to preferentially block presynaptic dopamine D2 and D3 autoreceptors and hence to enhance rather than inhibit dopaminergic neurotransmission. It is taken by mouth.
