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

thumb|class=skin-invert-image|Dopamine receptor flow chart

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, D<sub>1</sub> receptors have been found in the kidney

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

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 diseasethumb|class=skin-invert-image
  • Extrapyramidal 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 D<sub>2</sub> receptor blockade. 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 D<sub>2</sub> as a partial agonist but antagonizes D<sub>3.</sub> In addition, aripiprazole treats schizophrenia, bipolar disorder (mania), depression,
  • Loxapine binds D<sub>2</sub>, D<sub>3</sub> and D<sub>4</sub> with high affinity; can also bind D<sub>1.</sub> Loxapine is often used to treat agitated and violent patients with neuropsychiatric disorders such as bipolar disorder and schizophrenia.
  • Nemonapride binds D<sub>3</sub>, D<sub>4</sub> and D<sub>5.</sub>
  • Paliperidone binds D<sub>2</sub>, D<sub>3</sub> and D<sub>4</sub> with high affinity; can also bind D<sub>1</sub> and D<sub>5</sub>.
  • Remoxipride binds D<sub>2</sub> receptors with relatively low affinity.
  • Ziprasidone blocks the D<sub>2</sub> receptor and is used to treat schizophrenia, depression and bipolar disorder.

Dopamine antagonists used to treat nausea and vomiting

  • Domperidone is a peripherally selective dopamine D<sub>2</sub> receptor antagonist used as an antiemetic, gastroprokinetic agent and galactagogue.
  • Bromopride binds enteric D<sub>2</sub> receptors and also treats gastroparesis.
  • Nafadotride binds D<sub>2</sub> and D<sub>3</sub>

Other dopamine antagonists

  • Mesdopetam is under development for levodopa-induced dyskinesia and psychosis in people with Parkinson's disease

References