Droxidopa hydrochloride (200 mg/kg; i.p.) changes dopamine neuronal and prefrontal cortical activity and improves attention-deficit/hyperactivity disorder-like behavior in rats [2]. Droxidopa hydrochloride (10, 20 mg/kg; intraperitoneal injection) significantly enhanced the paw withdrawal latency at 5 weeks postoperatively and decreased mechanical hypersensitivity to thermal stimulation in rats with 6-OHDA damage [3].

Animal/Disease Models: 250-380g male SD (SD (Sprague-Dawley)) rats [2]
Doses: 200 mg/kg (10 mg/kg, intraperitoneal (ip) injection of benserazide 20 or 30 minutes before injection of L-DOPS)
Route of Administration: intraperitoneal (ip) injection
Experimental Results: At 30 minutes (P < 0.01) and 40 minutes (P < 0.05) after injection, the hyperactivity of BZ-pretreated SHR/NCrl was Dramatically diminished, the inattentive behavior of SHR/NCrl was improved, and the inattentive behavior of SHR/NCrl was improved. and SHR/NCrl's impulsive behavior improved. Wistar rat.

Absorption, Distribution and Excretion
Oral bioavailability is 90%. Drozidopa is primarily excreted in the urine, with its main metabolite being 3-O-methyldihydroxyphenylserine. Metabolism/Metabolites Drozidopa is metabolized by aromatic L-amino acid decarboxylases. Biological Half-Life 2-3 hours.

Hepatotoxicity

No abnormal liver function has been reported in patients taking drosidopa, but the clinical use of this drug is limited. No cases of clinically significant liver injury were reported in drosidopa pre-registration trials, and no published reports of drosidopa hepatotoxicity have been found since its approval. Therefore, drosidopa-induced liver injury, even if it occurs, is likely to be very rare.
Probability score: E (Unlikely to be the cause of clinically significant liver injury).

[1]. Horacio Kaufmann, et al. Droxidopa for neurogenic orthostatic hypotension. Neurology, 2014; 83(4).
[2]. Dela Peña I, et al. Droxidopa alters dopamine neuron and prefrontal cortex activity and improves attention-deficit/hyperactivity disorder-like behaviors in rats. Eur J Pharmacol. 2021 Feb 5;892:173826.
[3]. Cao LF, et al. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease. Neural Plast. 2016;2016:6383240.
[4]. Kaufmann H. L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience. Clin Auton Res. 2008 Mar;18 Suppl 1:19-24.

Dopamine (Droxidopa) is a serine derivative with its β-position replaced by a 3,4-dihydroxyphenyl group. As a prodrug of norepinephrine, it is used to treat neurogenic orthostatic hypotension. It has multiple functions as a prodrug, vasoconstrictor, and antihypertensive drug. It is an L-tyrosine derivative belonging to the catecholamine class of drugs. Dopamine is a prodrug of norepinephrine used to treat Parkinson's disease. It has been approved for marketing in Japan and is currently undergoing clinical trials in the United States. Its racemic form (dl-threo-3,4-dihydroxyphenylserine) has also been used to treat orthostatic hypotension and related studies have been conducted. Parkinson's disease patients have deficiencies in both norepinephrine and dopamine, which some studies suggest may be a potential cause of sudden transient rigidity in patients with advanced Parkinson's disease. Although levodopa (L-DOPS) has been used in Japan and Southeast Asia for some time, it is currently undergoing phase III clinical trials in the United States, Canada, Australia, and throughout Europe. If L-DOPS successfully completes clinical trials, it could be approved as early as 2011 for the treatment of neurogenic orthostatic hypotension (NOH). Furthermore, a Phase II clinical trial for the treatment of hypotension during dialysis is also underway. Chelsea Therapeutics, the US-based developer of L-DOPS, has received Orphan Drug Designation (ODS) for L-DOPS in the US for the treatment of NOH and diseases associated with Parkinson's disease, pure autonomic failure, and multiple system atrophy.
Droxidopa's physiological action is achieved by raising blood pressure.
Droxidopa is an orally effective norepinephrine prodrug used to treat symptomatic orthostatic hypotension caused by neurogenic autonomic failure. Dopamine (Droxidopa) has limited clinical use, but it has not been found to be associated with elevated serum enzymes or clinically significant acute liver injury.
Dopamine is a synthetic prodrug of norepinephrine used to treat Parkinson's disease and orthostatic hypotension.
See also: Norepinephrine (with active fraction). Drug Indications This drug is used to treat neurogenic orthostatic hypotension (NOH) associated with a variety of diseases, including multiple system atrophy, familial amyloid polyneuropathy, hypotension induced by hemodialysis, and Parkinson's disease. It has also been investigated for use in the treatment of neurological disorders, kidney diseases, blood disorders (hematopoietic organ diseases, not specifically described), and vertigo/syncope. Mechanism of Action Dopamine crosses the blood-brain barrier and is decarboxylated to norepinephrine by L-aromatic amino acid decarboxylases. Norepinephrine acts on α-adrenergic receptors, acting as a vasoconstrictor; it acts on β-adrenergic receptors, acting as a cardiac stimulant and arterial vasodilator.

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Pharmacodynamics
Dopamine (Droxidopa) is an orally effective synthetic norepinephrine precursor that can increase the norepinephrine deficiency in NOH patients, thereby improving orthostatic hypotension, and relieving related symptoms such as dizziness, vertigo, blurred vision and syncope by inducing tachycardia (increased heart rate) and hypertension.

C9H11NO5

213.187342882156

249.04

1260173-94-1

Droxidopa;23651-95-8

92974

Typically exists as solid at room temperature

1.045

5

6

3

15

235

2

O[C@H](C1C=CC(=C(C=1)O)O)[C@@H](C(=O)O)N

QXWYKJLNLSIPIN-JGVFFNPUSA-N

InChI=1S/C9H11NO5/c10-7(9(14)15)8(13)4-1-2-5(11)6(12)3-4/h1-3,7-8,11-13H,10H2,(H,14,15)/t7-,8+/m0/s1

(2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)