Dopamine receptor antagonist
Dopaminergic blockers
Drug class
Haloperidol
Class identifiers
UseSchizophrenia, bipolar disorder, nausea and vomiting, etc.
ATC codeN05A
Biological targetDopamine receptors
External links
MeSHD012559
Legal status
In Wikidata

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.[1] Several other dopamine antagonists are antiemetics used in the treatment of nausea and vomiting.

Receptor pharmacology

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.[2] The D1-like class of dopamine receptors is coupled to Gαs/olf and stimulates adenylate cyclase production, whereas the D2-like class is coupled to Gαi/o and thus inhibits adenylate cyclase production.[2]

D1-like receptors: D1 and D5

D1-like receptors – D1 and D5 are always found post-synaptically. The genes coding these receptors lack introns, so there are no splice variants.

D1 receptors

D5 receptors

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 receptors

D3 receptors

D4 receptors

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.[5] Furthermore, most effective antipsychotics block D2 receptors, suggesting a role for dopamine in schizophrenia.[5][6][7] Additional studies hypothesize dopamine dysregulation is involved in Huntington's disease, ADHD, Tourette's syndrome, major depression, manic depression, addiction, hypertension and kidney dysfunction.[5][7][8] Dopamine receptor antagonists are used for some diseases such as schizophrenia, bipolar disorder, nausea and vomiting.[5]

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:

Examples

First-generation antipsychotics (typical)

First generation antipsychotics are used to treat schizophrenia and are often accompanied by extrapyramidal side effects.[19] They inhibit dopaminergic neurotransmission in the brain by blocking about 72% of the D2 dopamine receptors.[20] They can also block noradrenergic, cholinergic, and histaminergic activity.[20]

Chemical Structure of typical antipsychotic chlorpromazine

Second-generation antipsychotics (atypical)

These drugs are not only dopamine antagonists at the receptor specified, but also act on serotonin receptor 5HT2A.[20][25] These drugs have less extrapyramidal side effects and are less likely to affect prolactin levels when compared to typical antipsychotics.[26]

Clozapine

Dopamine antagonists used to treat nausea and vomiting

Antagonists used only in research settings

References

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