Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the DRD2gene. 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 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 all antipsychotic drugs.
The long form (D2Lh) has the "canonical" sequence and functions as a classic post-synaptic receptor. The short form (D2Sh) is pre-synaptic and functions as an autoreceptor that regulates the levels of dopamine in the synaptic cleft.Agonism of D2sh receptors inhibits dopamine release; antagonism increases dopaminergic release. A third D2(Longer) form differs from the canonical sequence where 270V is replaced by VVQ.
-141C insertion/deletion The polymorphisms have been investigated with respect to association with schizophrenia.
Some researchers have previously associated the polymorphism Taq 1A (rs1800497) to the DRD2 gene. However, the polymorphism resides in exon 8 of the ANKK1 gene. DRD2 TaqIA polymorphism has been reported to be associated with an increased risk for developing motor fluctuations but not hallucinations in Parkinson's disease.
Most of the older antipsychotic drugs such as chlorpromazine and haloperidol are antagonists for the dopamine D2 receptor, but are, in general, very unselective, at best selective only for the "D2-like family" receptors and so binding to D2, D3 and D4, and often also to many other receptors such as those for serotonin and histamine, resulting in a range of side-effects and making them poor agents for scientific research. In similar manner, older dopamine agonists used for Parkinson's disease such as bromocriptine and cabergoline are poorly selective for one dopamine receptor over another, and, although most of these agents do act as D2 agonists, they affect other subtypes as well. Several selective D2ligands are, however, now available, and this number is likely to increase as further research progresses.
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