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Dopamine antagonist

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 have been used in treating schizophrenia, bipolar disorder, and stimulant psychosis. Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

Receptor pharmacology
Dopamine receptors are all G protein–coupled receptors, and are divided into two classes based on which G-protein they are coupled to. as well as substantia nigra, In addition, D1 receptors have been found in the kidney D5 receptors • Low levels of D5 receptors have been found in the hypothalamus, prefrontal cortex and cingulate cortex; as well as memory areas such as hippocampus, dentate gyrus and entorhinal cortex. • In addition, D5 receptors have been found in the kidney D2-like receptors: D2, D3 and D4 D2-like receptors – unlike the D1-like class, these receptors are found pre and post-synaptically. The genes that code these receptors have introns, leading to many alternately spliced variants. D2 receptorsD2 receptors are found in the striatum, substantia nigra, ventral tegmental area, hypothalamus, cortex, septum, amygdala, hippocampus, and olfactory tubercle. • These receptors have also been found in the retina and pituitary gland. • Peripherally, these receptors have been found in the renal, mesenteric, and splenic arteries as well as on the adrenal cortex and medulla and within the kidney. D3 receptorsD3 receptors are highly expressed on neurons in islands of Calleja and nucleus accumbens shell and lowly expressed in areas such as the substantia nigra pars compacta, hippocampus, septal area, and ventral tegmental area. • Additional studies have found these receptors peripherally in the kidney D4 receptorsD4 receptors are found in amygdala, hippocampus, hypothalamus, globus pallidus, substantia nigra pars reticula, the thalamus, the retina and the kidney ==Implications in disease==
Implications in disease
The dopaminergic system has been implicated in a variety of disorders. Parkinson's disease results from loss of dopaminergic neurons in the striatum. Dopamine receptor antagonists are used in the management of a broad range of diseases and conditions such as schizophrenia, bipolar disorder, nausea and vomiting. as part of normal circadian rhythm functions, and pathological imbalances have been implicated in Parkinson's disease ==Side effects==
Side effects
They may include one or more of the following and last indefinitely even after cessation of the dopamine antagonist, especially after long-term or high-dosage use: • Cardiovascular diseaseExtrapyramidal symptoms (EPS) associated with typical antipsychotics: • Early stage – occurs at onset of treatment or following increased dose, patients recover when dose is decreased • Acute dystonias • Increased appetite including increased craving and binge eating that lead to weight gain • Increased risk for insulin resistance is a medical emergency caused by a decrease in dopaminergic activity, resulting in a central D2 receptor blockade. ==Examples==
Examples
First-generation antipsychotics (typical) First generation antipsychotics are used to treat schizophrenia and are often accompanied by extrapyramidal side effects. They can also block noradrenergic, cholinergic, and histaminergic activity. It is absorbed very easily and has a high first pass effect. and is used to treat bipolar disorder and schizophrenia. Its side effects include weight gain but there is lower risk for orthostatic hypotension and hyperprolactinemia. • Aripiprazole binds D2 as a partial agonist but antagonizes D3. In addition, aripiprazole treats schizophrenia, bipolar disorder (mania), depression, • Loxapine binds D2, D3 and D4 with high affinity; can also bind D1. Loxapine is often used to treat agitated and violent patients with neuropsychiatric disorders such as bipolar disorder and schizophrenia. • Nemonapride binds D3, D4 and D5. • Paliperidone binds D2, D3 and D4 with high affinity; can also bind D1 and D5. • Remoxipride binds D2 receptors with relatively low affinity. • Ziprasidone blocks the D2 receptor and is used to treat schizophrenia, depression and bipolar disorder. Dopamine antagonists used to treat nausea and vomitingDomperidone is a peripherally selective dopamine D2 receptor antagonist used as an antiemetic, gastroprokinetic agent and galactagogue. • Bromopride binds enteric D2 receptors and also treats gastroparesis. • Nafadotride binds D2 and D3 Other dopamine antagonistsMesdopetam is under development for levodopa-induced dyskinesia and psychosis in people with Parkinson's disease ==References==
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