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 D2
ligands are, however, now available, and this number is likely to increase as further research progresses.
Agonists •
Bromocriptine – full agonist •
Cabergoline (Dostinex) •
N,N-Propyldihydrexidine – analogue of the D1/D5 agonist
dihydrexidine; Selective for postsynaptic D2 receptor over the presynaptic D2
autoreceptor. •
Piribedil – also D3 receptor agonist and
α2–adrenergic antagonist •
Pramipexole – also D3, D4 receptor agonist •
Quinagolide (Norprolac) •
Quinelorane – affinity for D2 > D3 •
Quinpirole – also D3 receptor agonist •
Ropinirole – full agonist •
Sumanirole – full agonist; highly selective •
Talipexole – selective for D2 over other dopamine receptors, but also acts as α2–adrenoceptor agonist and 5-HT3 antagonist.
Partial agonists •
Aplindore •
Aripiprazole •
Armodafinil – although primarily thought to be a weak DAT inhibitor, armodafinil is also a D2 partial agonist. •
Modafinil - The (R)-(−)-enantiomer, known as Armodafinil in its pure form •
Ketamine (also NMDA antagonist) •
LSD – in vitro, LSD was found to be a partial agonist and potentiates dopamine-mediated prolactin secretion in lactotrophs. LSD is also a 5-HT2A agonist. •
OSU-6162 – also 5-HT2A partial agonist, acts as "dopamine stabilizer" •
Roxindole (only at the D2 autoreceptors) •
Brilaroxazine(
RP5063) •
Salvinorin A – also
κ-opioid agonist. •
Memantine – Also
NMDA antagonist Antagonists •
Atypical antipsychotics (except aripiprazole, brexpiprazole, and any other D2 receptor partial agonists) •
Cinnarizine •
Chloroethylnorapomorphine •
Desmethoxyfallypride •
Domperidone – D2 and D3 antagonist; does not cross the blood-brain barrier •
Mesdopetam •
Metoclopramide – Antiemetic, crosses blood-brain barrier. Causes drug-induced Parkinsonism. •
Eticlopride •
Fallypride •
Hydroxyzine (Vistaril, Atarax) •
Itopride •
L-741,626 – 4-phenylpiperidine (such as haloperidol), highly selective D2 inverse agonist •
ST-148 (D2L antagonist) - D2L selective antagonist • 11C-radiolabeled
Raclopride – commonly employed in
positron emission tomography studies •
Typical antipsychotics • SV 293 •
Yohimbine •
Buspirone D2 presynaptic autoreceptors (low dose) and postsynaptic D2 receptors (at higher doses) antagonist ;
D2sh selective (presynaptic autoreceptors) •
Amisulpride (low doses) •
CGP-25454A •
Sulpiride •
UH-232 Allosteric modulators •
Homocysteine – negative
allosteric modulator •
PAOPA •
SB269652 Heterobivalent ligands • 1-(6-(((
R,
S)-7-Hydroxychroman-2-yl)methylamino]hexyl)-3-((
S)-1-methylpyrrolidin-2-yl)pyridinium bromide (compound 2, D2R agonist and
nAChR antagonist)
Dual D2AR/ A2AAR ligands • Dual agonists for
A2AAR and D2AR receptors have been developed.
Functionally selective ligands • UNC9994 ==Protein–protein interactions==