Tolcapone (Synonyms: Ro 40-7592) |
| Catalog No.GC17921 |
A reversible COMT inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 134308-13-7
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Tolcapone is a novel, reversible and orally-bioavailable small-molecule catechol-O-methyltransferase (COMT) inhibitor used for as an adjunct to levodopa therapy for the treatment of Parkinson’s disease (PD). The chemical structure of tolcapone contains a catechol structure with two electron withdrawing substituents of a tendency to easily deliver a proton resulting in an anion that is highly affinitive for COMT (the value of 50% inhibition concentration IC50 of 36 nM in rat liver) and displaces other catechols (such as catecholamines and levodopa) from the COMT catalytic center to prevent methylation. Study results have that the use of tolcapone reduces the dosage but enhances the therapeutic effects of levodopa to control PD symptoms.
Reference
[1].Truong DD. Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. Clin Interv Aging. 2009;4:109-113
[2].Jorga K, Fotteler B, Heizmann P, Gasser R. Metabolism and excretion of tolcapone, a novel inhibitor of catechol-O-methyltransferase. Br J Clin Pharmacol. 1999; 48(4):513-520.
| Kinase experiment [1]: | |
|
COMT assay |
COMT activity was evaluated by the ability of homogenates to methylate adrenaline to metanephrine. Aliquots of 0.5 ml of the homogenate were preincubated for 20 min with 0.5 ml of phosphate buffer (0.5 mM); thereafter, the reaction mixture was incubated for 30 min with increasing concentrations of adrenaline (5 to 500 uM) in the presence of a saturating concentration (100 /M) of the methyl donor (S-adenosyl-L-methionine); the incubation medium contained also pargyline (100 gM), MgCl2 (100 gM) and EGTA (1 mM). The preincubation and incubation were carried out at 37°C, in conditions of light protection, with continuous shaking and without oxygenation. In experiments conducted with the aim of studying the inhibitory effect of tolcapone on COMT activity, tissue homogenates were preincubated for 15 min with increasing concentrations of tolcapone (0.5 to 10,000 nM); the incubation was performed in the presence of a concentration of adrenaline three times the corresponding Km value, as determined in saturation experiments for each age group. At the end of the incubation period the tubes were transferred to ice and the reaction was stopped by the addition of 100 ul of perchloric acid (2 M). The samples were then centrifuged (200 g, 4 min, 4C), and 500 Ml aliquots of the supernatant filtered on Millipore microfilters (MF1) were used for the assay of metanephrine. This procedure allows 99% extraction of catecholamines and their methylated metabolites. |
| Cell experiment [2]: | |
|
Cell lines |
SH-SY5Y neuroblastoma cells |
|
Preparation method |
Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reaction Conditions |
6 days |
|
Applications |
Tolcapone as an inhibitor of COMT shows a protective effect against HIV associated dendritic and synaptic damage. |
| Animal experiment [3]: | |
|
Animal models |
Male albino rats (Fii-albino, 270-300 g) |
|
Dosage form |
Orally in a final volume of 2 ml/kg. |
|
Preparation method |
Suspended in saline containing 1% Tween 80 using a glass homogenizer. |
|
Applications |
Tolcapone is very effective in increasing the striatal extracellular levels of L-DOPA and dopamine in the rat, when given in combination with L-DOPA+benserazide. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: 1. Vieira-Coelho MA, Soares-da-Silva P. Ontogenic aspects of liver and kidney catechol-O-methyltransferase sensitivity to tolcapone. Br J Pharmacol. 1996 Feb;117(3):516-520. 2. Lee TT, Chana G, Gorry PR etc. Inhibition of catechol-O-methyl transferase (COMT) by tolcapone restores reductions in microtubule-associated protein 2 (MAP2) and synaptophysin (SYP) following exposure of neuronal cells to neurotropic HIV. J Neurovirol. 2015 Jun 3. 3. Napolitano A, Zürcher G, Da Prada M. Effects of tolcapone, a novel catechol-O-methyltransferase inhibitor, on striatal metabolism of L-dopa and dopamine in rats. Eur J Pharmacol. 1995 Feb 6;273(3):215-21. |
|
| Cas No. | 134308-13-7 | SDF | |
| Synonyms | Ro 40-7592 | ||
| Chemical Name | (3,4-dihydroxy-5-nitrophenyl)-(4-methylphenyl)methanone | ||
| Canonical SMILES | CC1=CC=C(C=C1)C(=O)C2=CC(=C(C(=C2)O)O)[N+](=O)[O-] | ||
| Formula | C14H11NO5 | M.Wt | 273.24 |
| Solubility | ≥ 12mg/mL in DMSO, ≥ 5.78 mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.6598 mL | 18.2989 mL | 36.5979 mL |
| 5 mM | 0.732 mL | 3.6598 mL | 7.3196 mL |
| 10 mM | 0.366 mL | 1.8299 mL | 3.6598 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *