| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
| Targets |
MAO
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| 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. This study investigated the monoamine oxidase (MAO) A and B inhibitory activities of rasagiline [N-propynyl-1R(+)-aminoindene] and its S(-)-enantiomer (TVP 1022) and racemic compound (AGN-1135) in rats, and compared them with selegiline (1-deprazole). The MAO-inhibiting tissues studied included the brain, liver, and small intestine. 2. Rasagiline and AGN-1135 exhibited highly potent selective irreversible MAO inhibitory activities both in vitro and in vivo, while the S(-) enantiomer showed relatively low activity in the studied tissues. 3. The in vitro IC50 values of rasagiline for MAO activity in rat brain were 4.43 ± 0.92 nM (type B) and 412 ± 123 nM (type A), respectively. Following a single administration of rasagiline, the in vitro ED50 values for MAO-B inhibition in the brain and liver were 0.1±0.01 and 0.042±0.0045 mg kg⁻¹, respectively, while the in vitro ED50 values for MAO-A inhibition were 6.48±0.81 and 2.38±0.35 mg kg⁻¹, respectively. 4. After long-term (21 days) oral administration, the selective inhibition of MAO-B in the liver and brain was maintained, with ED50 values of 0.014±0.002 and 0.013±0.001 mg kg⁻¹, respectively. 5. Rasagiline's selectivity for MAO-B relative to MAO-A is similar to that of selegiline. In acute or chronic administration, rasagiline's inhibitory potency against MAO-B in the rat brain and liver is 3 to 15 times that of selegiline, but their in vitro potency is similar. 6. These data, along with the fact that rasagiline does not enhance tyramine-like sympathomimetic effects at selective MAO-B inhibitory doses, suggest that this inhibitor, like selegiline, may be an effective treatment for Parkinson's disease, for symptomatic treatment or as adjunctive therapy with levodopa. However, rasagiline does not produce amphetamine-like metabolites, which may be one of its therapeutic advantages. [1]
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| Molecular Formula |
C12H13N
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|---|---|
| Molecular Weight |
171.2383
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| Exact Mass |
171.105
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| Elemental Analysis |
C, 84.17; H, 7.65; N, 8.18
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| CAS # |
185517-74-2
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| Related CAS # |
(S)-Rasagiline mesylate;202464-88-8; 136236-51-6; 161735-79-1
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| PubChem CID |
5289310
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| Appearance |
Light yellow to yellow solid powder
|
| Vapour Pressure |
0.000816mmHg at 25°C
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| LogP |
2.287
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
13
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| Complexity |
212
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C#CCN[C@H]1CCC2=CC=CC=C12
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| InChi Key |
RUOKEQAAGRXIBM-LBPRGKRZSA-N
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| InChi Code |
InChI=1S/C12H13N/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12/h1,3-6,12-13H,7-9H2/t12-/m0/s1
|
| Chemical Name |
(1S)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine
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| Synonyms |
185517-74-2; (S)-N-(2-Propynyl)-2,3-dihydroinden-1-amine; TVP1022; N-PROPARGYL-1(S)-AMINOINDAN; (S)-Rasagiline; (1S)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine; MFCD09029306; S-PAI;
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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) |
DMSO : ~100 mg/mL (~583.98 mM)
Ethanol : ~100 mg/mL (~583.98 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (14.60 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 25.0 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: ≥ 2.5 mg/mL (14.60 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.8398 mL | 29.1988 mL | 58.3976 mL | |
| 5 mM | 1.1680 mL | 5.8398 mL | 11.6795 mL | |
| 10 mM | 0.5840 mL | 2.9199 mL | 5.8398 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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