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| Targets |
D1-like dopamine receptors (D1 and D5). Dihydrexidine is a full agonist at D1 and D5 receptors with similar affinity for both, and approximately 10-fold selectivity over D2-like receptors. IC₅₀ = 10 nM for D1 receptors.
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| ln Vitro |
In U2OS cells, dioxyxidine hydrochloride (DAR-0100) significantly raises YAP phosphorylation [5].
In vitro, dihydrexidine HCl is a potent, selective, and full efficacy D1-like dopamine receptor agonist with an IC₅₀ of 10 nM for D1 receptors. It has similar affinity for D1 and D5 and roughly 10-fold selectivity over D2-like receptors. The compound's structural configuration allows it to mimic the action of dopamine, activating downstream signaling pathways associated with dopamine receptor activation. It also stimulates YAP phosphorylation. |
| ln Vivo |
Dioxyxidine hydrochloride has a half-life of one to two hours and a poor oral bioavailability [3]. A notable dopamine D1 receptor agonist activity is produced by dioxyxidine hydrochloride (3 mg/kg; ip) [4].
Dihydrexidine HCl has potent anti-Parkinsonian activity in vivo. As a full D1-like dopamine receptor agonist, it activates D1-mediated signaling pathways and produces effects consistent with dopamine receptor stimulation. The compound's efficacy in activating D1-mediated pathways supports its potential for treating disorders involving dopaminergic dysfunction such as Parkinson's disease. |
| Enzyme Assay |
In vitro dopamine receptor binding assays for dihydrexidine HCl use radioligand binding techniques with membrane preparations from cells expressing recombinant D1, D5, or D2-like dopamine receptors. Radiolabeled selective dopamine receptor ligands (such as [³H]-SCH23390 for D1-like or [³H]-raclopride for D2-like) are used as tracers. Competition binding experiments determine binding affinity (Ki) and selectivity.
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| Cell Assay |
In vitro cell-based functional assays for dihydrexidine HCl evaluate its agonist activity at D1-like dopamine receptors using cAMP accumulation assays. Cells expressing recombinant D1 or D5 receptors are treated with the compound, and intracellular cAMP levels are measured. The compound's ability to stimulate cAMP production, its potency (EC₅₀), and its efficacy relative to dopamine are determined.
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| Animal Protocol |
Animal/Disease Models: Adult male Sprague–Dawley rats (275-300 g) [4]
Doses: 3 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Produce significant dopamine D1 receptor agonist effect in vivo. In vivo animal studies for dihydrexidine HCl have been conducted in models of Parkinson's disease and other dopamine-related disorders. The compound is administered systemically (typically intraperitoneally or intravenously), and behavioral endpoints such as locomotor activity, rotational behavior in unilateral lesioned models, or cognitive performance are assessed. These studies confirm the compound's anti-Parkinsonian activity. |
| ADME/Pharmacokinetics |
Dihydrexidine HCl has a molecular weight of approximately 273.76 g/mol (free base). The hydrochloride salt form is used for improved aqueous solubility. Detailed pharmacokinetic parameters such as half-life, bioavailability, and blood-brain barrier penetration are not extensively reported in the provided literature. The compound is soluble in DMSO and other organic solvents.
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| Toxicity/Toxicokinetics |
Specific toxicity data for dihydrexidine HCl is not extensively reported. As a potent D1-like dopamine receptor agonist, potential side effects may include those associated with dopaminergic stimulation such as dyskinesias, hypotension, and psychiatric effects. The compound is classified as a research-grade chemical and is not intended for human use.
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| References |
[1]. Lovenberg TW, et al. Dihydrexidine, a novel selective high potency full dopamine D-1 receptor agonist. Eur J Pharmacol. 1989 Jul 4;166(1):111-3.
[2]. Mottola DM, et al. Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist. J Pharmacol Exp Ther. 1992 Jul;262(1):383-93. [3]. Salmi P,et al. Dihydrexidine--the first full dopamine D1 receptor agonist. CNS Drug Rev. 2004 Fall;10(3):230-42. [4]. Gleason, S. D., et al. Effects of dopamine D1 receptor agonists in rats trained to discriminate dihydrexidine. Psychopharmacology, 2006;186(1), 25–31. [5]. Yu FX, et al. Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. 2012;150(4):780-791. |
| Additional Infomation |
Dihydrexidine hydrochloride (DAR-0100 hydrochloride) is a potent, selective, and full efficacy D1-like dopamine receptor (D1/D5) agonist with an IC₅₀ of 10 nM for D1 receptors. It has similar affinity for D1 and D5 and approximately 10-fold selectivity over D2-like receptors. The compound has potent anti-Parkinsonian activity and stimulates YAP phosphorylation. It has not received FDA approval.
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| Molecular Formula |
C17H17NO2
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|---|---|
| Molecular Weight |
267.322384595871
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| Exact Mass |
303.102
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| CAS # |
137417-08-4
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| Related CAS # |
(+)-Dihydrexidine hydrochloride;158704-02-0;Dihydrexidine;123039-93-0
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| PubChem CID |
11957519
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
21
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| Complexity |
361
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CC2=CC(=C(C=C2[C@@H]3[C@@H]1NCC4=CC=CC=C34)O)O.Cl
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| InChi Key |
IJYUPBNUPIRQEP-SATBOSKTSA-N
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| InChi Code |
InChI=1S/C17H17NO2.ClH/c19-15-7-10-5-6-14-17(13(10)8-16(15)20)12-4-2-1-3-11(12)9-18-14;/h1-4,7-8,14,17-20H,5-6,9H2;1H/t14-,17-;/m1./s1
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| Chemical Name |
(6aR,12bS)-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine-10,11-diol;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~83.33 mg/mL (~274.31 mM)
H2O : ~10 mg/mL (~32.92 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7408 mL | 18.7042 mL | 37.4083 mL | |
| 5 mM | 0.7482 mL | 3.7408 mL | 7.4817 mL | |
| 10 mM | 0.3741 mL | 1.8704 mL | 3.7408 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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