Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1980, approximately 10 to 20 years after most of the other TCAs were introduced in the United States.
A dopamine antagonist, also known as an anti-dopaminergic and a dopamine receptor antagonist (DRA), 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.
Pindolol, sold under the brand name Visken among others, is a nonselective beta blocker which is used in the treatment of hypertension. It is also an antagonist of the serotonin 5-HT1A receptor, preferentially blocking inhibitory 5-HT1A autoreceptors, and has been researched as an add-on therapy to various antidepressants, such as clomipramine and the selective serotonin reuptake inhibitors (SSRIs), in the treatment of depression and obsessive-compulsive disorder.
Pramipexole, sold under the brand Mirapex among others, is a medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In Parkinson's disease it may be used alone or together with levodopa. It is taken by mouth. Pramipexole is a dopamine agonist of the non-ergoline class.
Lisuride, sold under the brand name Dopergin among others, is a monoaminergic medication of the ergoline class which is used in the treatment of Parkinson's disease, migraine, and high prolactin levels. It is taken by mouth.
Rotigotine, sold under the brand name Neupro among others, is a dopamine agonist of the non-ergoline class of medications indicated for the treatment of Parkinson's disease and restless legs syndrome. It is formulated as a once-daily transdermal patch which provides a slow and constant supply of the drug over the course of 24 hours.
Mesulergine (INNTooltip International Nonproprietary Name) (developmental code name CU-32085) is a drug of the ergoline group which was never marketed. It acts on serotonin and dopamine receptors. Specifically, it is an agonist of dopamine D2-like receptors and serotonin 5-HT6 receptors and an antagonist of serotonin 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors.. It also has affinity for the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT5A receptors. The compound had entered clinical trials for the treatment of Parkinson's disease; however, further development was halted due to adverse histological abnormalities in rats. It was also investigated for the treatment of hyperprolactinemia (high prolactin levels).
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.
The serotonin 1A receptor is a subtype of serotonin receptors, or 5-HT receptors, that binds serotonin, also known as 5-HT, a neurotransmitter. 5-HT1A is expressed in the brain, spleen, and neonatal kidney. It is a G protein-coupled receptor (GPCR), coupled to the Gi protein, and its activation in the brain mediates hyperpolarization and reduction of firing rate of the postsynaptic neuron. In humans, the serotonin 1A receptor is encoded by the HTR1A gene.
Dopamine receptor D3 is a protein that in humans is encoded by the DRD3 gene.
Sultopride (trade names Barnetil, Barnotil, Topral) is an atypical antipsychotic of the benzamide chemical class used in Europe, Japan, and Hong Kong for the treatment of schizophrenia. It was launched by Sanofi-Aventis in 1976. Sultopride acts as a selective D2 and D3 receptor antagonist. It has also been shown to have clinically relevant affinity for the GHB receptor as well, a property it shares in common with amisulpride and sulpiride.
WAY-100135 is a serotonergic drug of the phenylpiperazine family which is used in scientific research. It acts as potent 5-HT1A receptor antagonist, and was originally believed to be highly selective, but further studies have demonstrated that it also acts as a partial agonist of the 5-HT1D receptor (pKi = 7.58; virtually the same affinity for 5-HT1A), and to a much lesser extent, of the 5-HT1B receptor (pKi = 5.82). These findings may have prompted the development of the related compound WAY-100635, another purportedly selective and even more potent 5-HT1A antagonist, which was synthesized shortly thereafter. However, WAY-100635 turned out to be non-selective as well, having been shown to act additionally as a potent D4 receptor agonist later on.
S-15535 is a phenylpiperazine drug which is a potent and highly selective 5-HT1A receptor ligand that acts as an agonist and antagonist at the presynaptic and postsynaptic 5-HT1A receptors, respectively. It has anxiolytic properties.
Tiospirone (BMY-13,859), also sometimes called tiaspirone or tiosperone, is an atypical antipsychotic of the azapirone class. It was investigated as a treatment for schizophrenia in the late 1980s and was found to have an effectiveness equivalent to those of typical antipsychotics in clinical trials but without causing extrapyramidal side effects. However, development was halted and it was not marketed. Perospirone, another azapirone derivative with antipsychotic properties, was synthesized and assayed several years after tiospirone. It was found to be both more potent and more selective in comparison and was commercialized instead.
Sarizotan (EMD-128,130) is a selective 5-HT1A receptor agonist and D2 receptor antagonist, which has antipsychotic effects, and has also shown efficacy in reducing dyskinesias resulting from long-term anti-Parkinsonian treatment with levodopa.
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.
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.
