Mofegiline HCl (MDL-72,974; MDL72,974), the hydrochloride salt of Mofegiline, is a potent and irreversible inhibitor of monoamine oxidase B (MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) with the potential to be used for the treatment for various diseases.
Physicochemical Properties
| Molecular Formula | C11H14CLF2N |
| Molecular Weight | 233.6868 |
| Exact Mass | 233.078 |
| CAS # | 120635-25-8 |
| PubChem CID | 6446650 |
| Appearance | White to off-white solid powder |
| Boiling Point | 322.7ºC at 760 mmHg |
| Flash Point | 149ºC |
| Vapour Pressure | 0.00232mmHg at 25°C |
| LogP | 4.072 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 15 |
| Complexity | 184 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1=CC(=CC=C1CC/C(=C\F)/CN)F.Cl |
| InChi Key | QUCNNQHLIHGBIA-HCUGZAAXSA-N |
| InChi Code | InChI=1S/C11H13F2N.ClH/c12-7-10(8-14)2-1-9-3-5-11(13)6-4-9;/h3-7H,1-2,8,14H2;1H/b10-7+; |
| Chemical Name | (2E)-2-(fluoromethylidene)-4-(4-fluorophenyl)butan-1-amine;hydrochloride |
| Synonyms | MDL 72974A MDL72974A MDL-72974A |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | Rat brain mitochondrial MAO is inhibited by murfegiline hydrochloride (MDL72974A) in a concentration- and time-dependent manner[1]. In the rat striatum, murfegiline hydrochloride (MDL72974A) has a poor effect[2] but reduces [3H]GBR-12935 (1 nM) binding (IC50 >100 μM) and [3H]dopamine (15 nM) uptake (IC50 of 31.8 μM). The aortas of dogs, rats, cows, and humans are all susceptible to SSAO inhibition by murfegiline hydrochloride (MDL72974A), with IC50 values of 2 nM, 5 nM, 80 nM, and 20 nM, respectively [3]. |
| ln Vivo | Murfegiline hydrochloride (MDL72974A) has the capacity to block MPTP in a mouse neurotoxicity model and inhibit MAO-B activity in vitro in a rat model (1.25 mg/kg; i.p.; 18 hours prior to MPTP treatment) [1]. |
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (150-400 g)[1] Doses: Group 1: 0.1-2.5 mg/kg; Group 2: 0.05-5 mg/kg Route of Administration: po (oral gavage); single dose for group 1, as for group 2, one time/day for 14 days Experimental Results:demonstrated the inhibition effect on rat brain MAO-A and MAO-B with EC50s of 8 mg/kg and 0.18 mg/kg, respectively, in group 1. Resulted more potent efficacy on MAO-A inhibition in a daily dosed-manner (group 2) than single dose (group 1) manner, indicating a long half-life of Mofegiline hydrochloride. Animal/Disease Models: Mate SwissWebster (CF-W) mice (25-30 g)[1] Doses: 1.25 mg/kg Route of Administration: intraperitoneal (ip) injection; 18 hrs (hrs (hours)) prior to administration of MPTP (20 mg/kg; i.p.; 4 times for two-hourly intervals, for 8 days) Experimental Results:Rescued MPTP-induced decreases in striatal levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mice. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (150-400 g) injected with Tyramine (HY-W007606) (1.25-80 μg/kg; i.v.)[1] Doses: Group 1: 1.8, 9 mg/kg; Group 2: 0.1, 1 mg/kg Route of Administration: po (oral gavage); single dose for group 1, as for group 2, one time/day for 14 days Experimental Results:Did not Dramatically potentiate the cardiovascular effects of intraduodenally administered Tyramine (HY-W007606) in anaesthetised rats. |
| References |
[1]. MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease. J Neural Transm Park Dis Dement Sect. 1989;1(4):243-54. [2]. Effect of L-deprenyl, its structural analogues and some monoamine oxidase inhibitors on dopamine uptake. Neuropharmacology. 1994 Jun;33(6):763-8. [3]. Inhibition of a type B monoamine oxidase inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine (MDL-72974A), on semicarbazide-sensitive amine oxidases isolated from vascular tissues and sera of different species. Biochem Pharmacol. 1992 Ja. [4]. Novel carbamate metabolites of mofegiline, a primary amine monoamine oxidase B inhibitor, in dogs and humans. Drug Metab Dispos. 1994 Sep-Oct;22(5):738-49. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~110 mg/mL (~470.71 mM) H2O : ~25 mg/mL (~106.98 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (11.77 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 27.5 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: ≥ 2.75 mg/mL (11.77 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 27.5 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. Solubility in Formulation 3: ≥ 2.75 mg/mL (11.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10 mg/mL (42.79 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2792 mL | 21.3959 mL | 42.7917 mL | |
| 5 mM | 0.8558 mL | 4.2792 mL | 8.5583 mL | |
| 10 mM | 0.4279 mL | 2.1396 mL | 4.2792 mL |