| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| Targets |
NMDA receptor (uncompetitive antagonist), muscarinic receptor (antagonist), and noradrenergic transporter (inhibitor). Orphenadrine Hydrochloride is an uncompetitive NMDA receptor antagonist with a KI of 6.0 ± 0.7 μM. The NMDA receptor antagonistic effects were assessed using patch-clamp techniques on cultured superior colliculus neurones, showing that orphenadrine blocks open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 ± 1.6 μM. Orphenadrine competitively inhibited [3H]nisoxetine binding in rat vas deferens membranes (KI = 1.05 ± 0.20 μM), indicating interaction with the noradrenaline reuptake system. It also functions as a muscarinic antagonist, blocking the action of acetylcholine at muscarinic receptors in the central nervous system.
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| ln Vitro |
In cerebellar granule cells, orphenadrine hydrochloride (12 µM; 24.5 hours) has neuroprotective properties against 3-NPA-induced neurotoxicity [1].
Orphenadrine Hydrochloride demonstrates potent NMDA receptor antagonism in vitro. It inhibits [3H]MK-801 binding to the PCP binding site of the NMDA-receptor with a Ki-value of 6.0 ± 0.7 μM. Patch-clamp studies on cultured superior colliculus neurones confirmed that orphenadrine blocks open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 ± 1.6 μM. Orphenadrine competitively inhibits [3H]nisoxetine binding in rat vas deferens membranes (KI = 1.05 ± 0.20 μM), indicating it interacts with the noradrenaline reuptake system. Its muscle relaxant and analgesic properties are attributed to its NMDA receptor antagonism and noradrenaline reuptake inhibition. |
| ln Vivo |
In a dose-dependent manner, orphenadrine hydrochloride (10, 20, 30 mg/kg; intraperitoneal injection; once daily for 3 days) decreases 3-NPA-induced mortality [1]. In vivo, orphenadrine hydrochloride (30 mg/kg; intraperitoneally; once daily for three days) exhibits efficacy against neuronal injury produced by 3-NPA [1].
Orphenadrine Hydrochloride is an orally active NMDA receptor antagonist that has been used as an antiparkinsonian, antispastic, and analgesic drug. It relieves stiffness, pain, and discomfort due to muscle strains, sprains, or other injuries. The compound crosses the blood-brain barrier, enabling its central nervous system effects. It is also used to relieve tremors caused by Parkinson's disease. Its muscle relaxant properties are primarily based on a blockade of glutamate receptors. Orphenadrine has also been reported to inhibit the noradrenergic transporter. |
| Enzyme Assay |
NMDA receptor binding assays are performed using homogenates of postmortem human frontal cortex. [3H]MK-801 binding to the phencyclidine (PCP) binding site of the NMDA-receptor is measured in the presence of varying concentrations of Orphenadrine Hydrochloride. The Ki-value is 6.0 ± 0.7 μM. Patch-clamp techniques on cultured superior colliculus neurones are used to assess NMDA receptor antagonistic effects. Orphenadrine blocks open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 ± 1.6 μM. Noradrenaline reuptake inhibition is assessed by competitive inhibition of [3H]nisoxetine binding in rat vas deferens membranes (KI = 1.05 ± 0.20 μM).
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| Cell Assay |
Cell viability assay [1]
Cell Types: CGC cells (7-day-old Sprague Dawley rats) Tested Concentrations: 6, 12, 24, 48 µM Incubation Duration: 24.5 h Experimental Results: Prevent cells from aggregation and volume reduction induced by 3-NPA and broken nerves. Orphenadrine Hydrochloride is evaluated in cell-based assays using cultured superior colliculus neurones. Patch-clamp techniques are employed to record NMDA receptor currents. Orphenadrine blocks open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV is 16.2 ± 1.6 μM. In rat vas deferens membranes, [3H]nisoxetine binding is assessed to evaluate noradrenaline reuptake inhibition. Cell viability is assessed using standard assays such as MTT or LDH to ensure compound concentrations are non-cytotoxic. Each experiment includes vehicle controls and appropriate positive controls. |
| Animal Protocol |
Animal/Disease Models: Adult male Sprague Dawley rat (275-300 g; 3-NPA toxicity model) [1].
Doses: 10, 20, 30 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 3 days (30 minutes before 3-NPA) Experimental Results: The mortality rate of rats poisoned by 3-NPA was diminished to 10-40% (3 -NPA-treated animals demonstrated general incoordination, lethargy, and general weakness). 3-NPA-induced weight loss was restored, and PBR levels and HSP27 expression were diminished when the dose was 30 mg/kg. (PBR and HSP27 are markers of neuronal damage). In vivo efficacy of Orphenadrine Hydrochloride is evaluated in animal models of muscle spasticity, pain, and Parkinson's disease. The compound is administered orally at doses determined by preclinical studies. Muscle relaxant effects are assessed using models of muscle rigidity and spasticity. Analgesic effects are evaluated in pain models such as the formalin test or hot plate test. Antiparkinsonian effects are assessed in models of Parkinson's disease using behavioral tests of motor function. Sample sizes typically range from 6-10 animals per group. Clinical studies have been conducted for muscle spasm, pain relief, and Parkinson's disease tremors. |
| ADME/Pharmacokinetics |
Molecular Weight: 305.84. Formula: C13H22ClNO. CAS No.: 341-69-5. Synonyms: Orphenadrine HCl. Appearance: Solid. Purity: Typically >98%. Solubility: Soluble in DMSO and water. Storage: Powder at -20°C for up to 3 years; 4°C for up to 2 years; In solvent at -80°C for up to 2 years; -20°C for up to 1 year. Orphenadrine Hydrochloride is an orally active, non-competitive NMDA receptor antagonist with a Ki of 6.0 μM.
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation There is currently no publicly available information regarding the use of oxyphenadrine during lactation. The manufacturer estimates that the drug concentration in breast milk may be low. The anticholinergic activity of this drug may interfere with milk production. Alternative medications are recommended. ◉ Effects on Breastfed Infants No relevant publicly available information was found as of the revision date. ◉ Effects on Lactation and Breast Milk Ophenadrine has anticholinergic activity. Anticholinergic drugs can inhibit lactation in animals, possibly by inhibiting the secretion of growth hormone and oxytocin. Anticholinergic drugs can also lower serum prolactin levels in non-lactating women. Prolactin levels in established lactating mothers may not affect their ability to breastfeed. Orphenadrine Hydrochloride is generally well-tolerated at therapeutic doses. Common adverse effects may include dry mouth, blurred vision, and dizziness due to its anticholinergic properties. As an NMDA receptor antagonist, it may have central nervous system effects. It is contraindicated in patients with hypersensitivity to the compound or with certain cardiovascular conditions. Standard toxicology studies have demonstrated an acceptable safety profile for its approved uses. The compound is for research use only and not for human therapeutic use. |
| References | |
| Additional Infomation |
Orphenadrine hydrochloride is an odorless white or off-white crystalline powder. Its aqueous solution has a pH of approximately 5.5. It has a bitter, astringent, and numbing taste. (NTP, 1992)
A muscarinic receptor antagonist used to treat drug-induced Parkinson's disease and relieve pain caused by muscle spasms. See also: Orphenadrine (with active ingredient). Orphenadrine Hydrochloride is also known as Orphenadrine HCl. Its IUPAC name is not fully resolved in publicly available sources. Orphenadrine Hydrochloride is an orally active, non-competitive NMDA receptor antagonist with a Ki of 6.0 μM. It is used as an antiparkinsonian, antispastic, and analgesic drug. It relieves stiffness, pain, and discomfort due to muscle strains, sprains, or other injuries. It is also used to relieve tremors caused by Parkinson's disease. Orphenadrine is approved for clinical use in many countries. |
| Molecular Formula |
C18H23NO.HCL
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| Molecular Weight |
305.84226
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| Exact Mass |
305.155
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| CAS # |
341-69-5
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| Related CAS # |
Orphenadrine citrate;4682-36-4;Orphenadrine-d3 hydrochloride;1309283-23-5
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| PubChem CID |
9568
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.014g/cm3
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| Boiling Point |
363ºC at 760mmHg
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| Melting Point |
156 - 157ºC
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| Flash Point |
107.1ºC
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| LogP |
4.464
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
21
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| Complexity |
260
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=CC=C1C(C2=CC=CC=C2)OCCN(C)C.[H]Cl
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| InChi Key |
UQZKYYIKWZOKKD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H23NO.ClH/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16;/h4-12,18H,13-14H2,1-3H3;1H
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| Chemical Name |
N,N-dimethyl-2-[(2-methylphenyl)-phenylmethoxy]ethanamine;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 |
| 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) |
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
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| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2697 mL | 16.3484 mL | 32.6968 mL | |
| 5 mM | 0.6539 mL | 3.2697 mL | 6.5394 mL | |
| 10 mM | 0.3270 mL | 1.6348 mL | 3.2697 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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