| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
MAO
|
|---|---|
| ln Vitro |
Determination of MAO-A and -B inhibition in vitro [1]
MAO-A and -B activities were determined in rat brain homogenate in vitro following incubation with varying concentrations of rasagiline, TVP1022, and selegiline (Figure 2 and Table 1). The IC50 values calculated for each inhibitor are presented in Table 1. The optical enantiomers of N-propargyl-1-aminoindan can be seen to possess a striking degree of stereoselectivity, since the (−)-isomer (TVP 1022) is 1/3,800 as active as the (+)-isomer (rasagiline) for inhibition of MAO-B. Whereas rasagiline is 93 times more potent for inhibition of MAO-B than MAO-A, TVP 1022 shows little or no selectivity for MAO-A or -B. Rasagiline and selegiline had similar IC50 values for inhibition of MAO-B (P>0.05), but selegiline was significantly less potent than rasagiline for inhibition of MAO-A (P<0.01). In human tissue, there was no significant difference between the IC50 values for rasagiline and selegiline for inhibition of MAO-A or MAO-B (Table 1), and TVP 1022 was again seen to be largely devoid of inhibitory activity. The racemic form of N-propargyl-1-aminoindan (AGN 1135) had approximately half the potency of rasagiline, indicating that no interaction occurred between the optical isomers at the MAO active site (similar data were obtained in preliminary studies using rat tissue). [1] |
| Enzyme Assay |
Determination of MAO inhibitory activity in vitro [1]
The activities of MAO-A and -B were determined by the adapted method of Tipton & Youdim (1983). Rat or human cerebral cortical tissue was homogenized in 0.3 M sucrose (one part tissue to 20 parts sucrose) using a glass-teflon motor-driven homogenizer (brain and liver), or Ultraturrax (gut). The inhibitor under test was added to a suitable dilution of the enzyme preparation in 0.05 M phosphate buffer (pH 7.4) and incubated together with selegiline 0.1 μM (for determination of MAO-A) or clorgyline 0.1 μM (for determination of MAO-B). Incubation was carried on for 60 min at 37°C before addition of labelled substrates (14C-5-hydroxytryptamine creatinine disulphate 100 μM for determination of MAO-A, or 14C-phenylethylamine 10 μM for determination of MAO-B) and incubation continued for 30 or 20 min respectively. The reaction was then stopped by addition of citric acid (2 M). Radioactive metabolites were extracted into toluene/ethyl acetate (1 : 1 v v−1), a solution of 2,5-diphenyloxazole was added to a final concentration of 0.4% (w v−1), and metabolite content estimated by liquid scintillation counting. Activity in presence of drug was expressed as a percentage of that in control samples. [1] The preincubation was carried out in the presence of clorgyline or selegiline because phenylethylamine is also metabolized quite effectively by MAO-A (O'Carroll et al., 1983), leading to inhibition curves for MAO-B, which showed a plateau at about 80% inhibition with selegiline or rasagiline if MAO-A was not inactivated. For comparison between two inhibitors with potentially different inhibitory effects on MAO-A and MAO-B, therefore, it was thought necessary to employ the system in which opposite enzyme forms are inactivated before assay. |
| Animal Protocol |
Determination of inhibition of MAO activity in vivo [1]
In in vivo studies, drugs were administered orally by gavage (p.o.). The animals weighed 250 – 300 g at the time of killing. For estimation of in vivo inhibitory effect, varying doses of the inhibitors were administered to groups of five or six rats for the stated times, the animals were killed by decapitation, tissues removed and frozen at −20°C, and enzyme activity determined subsequently as above. Enzyme activity in drug-treated tissues were expressed as a percentage of that in control tissues. |
| References | |
| Additional Infomation |
1. Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine oxidase (MAO) A and B inhibitor activities in rats together with its S(-)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were the brain, liver and small intestine. 2. While rasagiline and AGN1135 are highly potent selective irreversible inhibitors of MAO in vitro and in vivo, the S(-) enantiomer is relatively inactive in the tissues examined. 3. The in vitro IC(50) values for inhibition of rat brain MAO activity by rasagiline are 4.43+/-0.92 nM (type B), and 412+/-123 nM (type A). The ED(50) values for ex vivo inhibition of MAO in the brain and liver by a single dose of rasagiline are 0.1+/-0.01, 0.042+/-0.0045 mg kg(-1) respectively for MAO-B, and 6.48+/-0.81, 2.38+/-0.35 mg kg(-1) respectively for MAO-A. 4. Selective MAO-B inhibition in the liver and brain was maintained on chronic (21 days) oral dosage with ED(50) values of 0.014+/-0.002 and 0.013+/-0.001 mg kg(-1) respectively. 5. The degree of selectivity of rasagiline for inhibition of MAO-B as opposed to MAO-A was similar to that of selegiline. Rasagiline was three to 15 times more potent than selegiline for inhibition of MAO-B in rat brain and liver in vivo on acute and chronic administration, but had similar potency in vitro. 6. These data together with lack of tyramine sympathomimetic potentiation by rasagiline, at selective MAO-B inhibitory dosage, indicate that this inhibitor like selegiline may be a useful agent in the treatment of Parkinson's disease in either symptomatic or L-DOPA adjunct therapy, but lack of amphetamine-like metabolites could present a therapeutic advantage for rasagiline.[1]
|
| Molecular Formula |
C13H17NO3S
|
|---|---|
| Molecular Weight |
267.3440
|
| Exact Mass |
267.093
|
| Elemental Analysis |
C, 58.40; H, 6.41; N, 5.24; O, 17.95; S, 11.99
|
| CAS # |
202464-88-8
|
| Related CAS # |
(S)-Rasagiline;185517-74-2; Rasagiline;136236-51-6;Rasagiline-13C3 mesylate;1391052-18-8;Rasagiline-13C3 mesylate racemic;1216757-55-9
|
| PubChem CID |
16666423
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
2.872
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
18
|
| Complexity |
305
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
S(C([H])([H])[H])(=O)(=O)O[H].N([H])(C([H])([H])C#C[H])C1([H])C2=C([H])C([H])=C([H])C([H])=C2C([H])([H])C1([H])[H]
|
| InChi Key |
JDBJJCWRXSVHOQ-YDALLXLXSA-N
|
| InChi Code |
InChI=1S/C12H13N.CH4O3S/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12;1-5(2,3)4/h1,3-6,12-13H,7-9H2;1H3,(H,2,3,4)/t12-;/m0./s1
|
| Chemical Name |
methanesulfonic acid;(1S)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine
|
| Synonyms |
(S)-Rasagiline Mesylate; 202464-88-8; 202464-89-9; TVP1022 (mesylate); TVP1022 mesylate; methanesulfonic acid;(1S)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine; (1S)-N-(prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine; methanesulfonic acid; (S)-N-(PROP-2-YN-1-YL)-2,3-DIHYDRO-1H-INDEN-1-AMINE METHANESULFONATE;
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
|
|---|---|
| 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 | 3.7406 mL | 18.7028 mL | 37.4056 mL | |
| 5 mM | 0.7481 mL | 3.7406 mL | 7.4811 mL | |
| 10 mM | 0.3741 mL | 1.8703 mL | 3.7406 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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