Dopamine Receptor Agonist

Adrogolide hydrochloride (ABT-431 hydrochloride) is a chemically stable prodrug that can convert to the dopamine D1 receptor agonist A-86929. Adrogolide hydrochloride ameliorates the MPTP (HY-15608)-induced Parkinson's Disease in marmoset model, reduces the dyskinesias tendency. Adrogolide hydrochloride reverses Risperidone (HY-11018)-induced cognitive deficits in monkey.

Roxindole hydrochloride (EMD 38362), an indot-alkyl-pipenidine, is a potent agonist at dopamine autoreceptors, with an affinity for the D2-like subtype in the low nanomolar range. Roxindole can be used for the research of positive and negative schizophrenic symptoms. Roxindole is a 5-HT_1A agonist and 5-HT uptake inhibitor with high affinity for 5-HT_1A (IC₅₀=0.9 nM). Antipsychotic and antidepressant activities.

Sarizotan (EMD 128130) is an orally active serotonin 5-HT_1A receptor and dopamine receptor agonist. Sarizotan (EMD 128130) exhibits IC₅₀ values of 6.5 nM (rat 5-HT_1A), 0.1 nM (human 5-HT_1A), 15.1 nM (rat D₂), 17 nM (human D₂), 6.8 nM (human D₃) and 2.4 nM (human D_4.2), respectively.

ML417 is a selective and brain penetrant D3 dopamine receptor (D3R) agonist, with an EC₅₀ of 38 nM. ML417 potently promotes D3R-mediated β-arrestin translocation, G protein mediated signaling, and pERK phosphorylation with minimal effects on other GPCR-mediated signaling. ML417 exhibits neuroprotection against toxin-induced neurodegeneration of dopaminergic neurons.

UNC9994, an analog of Aripiprazole, is a functionally selective β-arrestin-biased dopamine D2 receptor (D2R) agonist with EC₅₀ <10 nM for β-arrestin-2 recruitment to D2 receptors. UNC9994 is simultaneously partial agonists of β-arrestin-2 translocation and antagonists of G_i-regulated cAMP production. Antipsychotic Activity.

Ropinirole (SKF 101468) is an orally active, potent D₃/D₂ receptor agonist with a K_i of 29 nM for D₂ receptor. Ropinirole has pEC₅₀s of 7.4, 8.4 and 6.8 for hD₂, hD₃ and hD₄ receptors, respectively. Ropinirole has no affinity for the D₁ receptors. Ropinirole has the potential for Parkinson's disease.

SKF 77434 hydrobromide is a selective dopamine D1 receptor partial agonist. SKF 77434 hydrobromide has the potential to study cocaine addiction.

SKF 83822 is an atypical agonist of dopamine D1 receptor. SKF 83822 activates adenylyl cyclase (AC), but not phospholipase C (PLC). SKF 83822 is also proved to stimulate AC via cAMP production. SKF 83822 can be used for research of schizophrenia.

Brilaroxazine (RP5603) is a potent and orally active multimodal dopamine (DA)/serotonin (5-HT) modulator. Brilaroxazine is a partial agonist of dopamine (DA) D2, D3, and D4 receptors, 5-HT1A (K_i=1.5 nM) and 5-HT2A (K_i=2.5 nM), and has antagonist activity at 5-HT2B (K_i=0.19 nM), and 5-HT7 (K_i=2.7 nM) receptors. Brilaroxazine is an atypical antipsychotic agent, and has the potential to improve cognitive impairments in neuropsychiatric and neurological diseases in vivo.

Pergolide (LY127809 free base), an Ergoline derivative, is a potent and orally active dopamine D₁ and D₂ receptor agonist. Pergolide can be used for Parkinson's disease and hyperprolactinaemia research.

CY 208-243 is a selective dopamine D1 receptor agonist which exhibits antiparkinsonian activity.

A-412997 dihydrochloride is a selective dopamine D₄ receptor agonist. A-412997 dihydrochloride improves cognitive performance in rats and can be used in the research of psychiatric diseases.

N-(α-Linolenoyl) tyrosine (NLT) is a dopaminergic agonist capable of crossing the blood-brain barrier. N-(α-Linolenoyl) tyrosine increases the level, turnover rate and release amount of dopamine in the striatum. N-(α-Linolenoyl) tyrosine modulates rotational behavior in a rat model with unilateral striatal injury and alleviates excessive blinking symptoms in models induced by dopamine-depleting agents. N-(α-Linolenoyl) tyrosine can be used for research on Parkinson's disease and idiopathic blepharospasm.

(Rac)-Tavapadon ((Rac)-PF-06649751) is a potent and selective noncatechol dopamine D1 receptor agonist. (Rac)-Tavapadon displays potent full agonism in the GS activation assay as well as partial agonism in the β-arrestin2 recruitment assay (GS-cAMP, EC₅₀=0.8 nM; β-arrestin2, EC₅₀=68 nM). (Rac)-Tavapadon has antiparkinsonian activity.

Brexpiprazole-d₈ (OPC-34712-d₈) is the deuterium labeled Brexpiprazole (HY-15780). Brexpiprazole (OPC-34712), an atypical orally active antipsychotic agent, is a partial agonist of human 5-HT1A and dopamine D_2L receptor with K_is of 0.12 nM and 0.3 nM, respectively. Brexpiprazole is also a 5-HT2A receptor antagonist with a K_i of 0.47 nM. Brexpiprazole also shows potent antagonist activity at human noradrenergic α1B (K_i=0.17 nM) and α2C receptors (K_i=0.59 nM)^.

Naxagolide ((+)-PHNO; Dopazinol) is a potent dopamine D2 (Dopamine Receptor) agonist. Naxagolide has the potential for the research of parkinson's disease (PD).

Didesmethyl cariprazine is an orally active, BBB-permeable metabolite of Cariprazine (HY-14763). Didesmethyl cariprazine is a partial agonist at the D₂ and D₃ receptors, full agonist at the 5-HT_1A receptor, and antagonist at the human 5-HT_2B receptor (K_i: 1.41 nM (human D_2L), 0.056 nM (human D₃), 1.7 nM (human 5-HT_1A), 0.52 nM (human 5-HT_2B)). Didesmethyl cariprazine dose-dependently inhibits the spontaneous activity of rat midbrain dopaminergic neurons.

TDHL (Tergurid) is a dopamine receptor agonist with a K_d of 0.39 nM for D2 receptor and an orally available 5-HT-2 receptor antagonist.

D5R agonist 1 (Compound 5j) is a selective, orally active and BBB penetrable D5R partial agonist (EC₅₀: 269.7 nM). D5R agonist 1 enhances the cognition in the Scopolamine (HY-N0296)-induced amnesia model.

Talipexole (B-HT920) is a dopamine agonist that has been proposed as an antiparkinsonian agent.