| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Histamine H3 receptor (no specific IC50/Ki values provided in this review; the compound is described as an H3 inverse agonist/antagonist) [1]
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|---|---|
| ln Vitro |
MK-0249 (Compound 1) is a substrate for rat P-gp but not for human P-gp, and it exhibits very good hepatic clearance values (CLh e 11 mL/min/kg)[1]. MK-0249 exhibits a strong affinity for binding human, rat, and rhesus H3 receptors, as evidenced by its respective Ki values of 6.8 ± 1.3 nM, 33 ± 3 nM, and 4.3 ± 1.2 nM[1]. High intrinsic activity is displayed by MK-0249[1].
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| ln Vivo |
The rat brain's histamine levels are raised by MK-0249 (Compound 1) (0-30 mg/kg; po; once) in a dose-dependent way[1]. In comparison to mdr1a (+/+) mice, mdr1a (-/-) mice exhibit significantly greater brain penetrability and a lower plasma Occ90 value when exposed to MK-0249 (10 mg/kg; po; once)[1]. In rodents, P-gp mediated efflux greatly limits MK-0249, whereas in humans, this efflux should be very minor or nonexistent[1]. MK-0249 exhibits rat brain permeability.
In a phase 2 clinical trial, MK-0249 at 10 mg daily for 4 weeks failed to improve cognitive performance in schizophrenic patients receiving standard antipsychotic medication, despite achieving >85% H3 receptor occupancy. [1] In a PET study in healthy volunteers, MK-0249 at doses of 2.5 to 50 mg achieved H3 receptor occupancy in the striatum up to 93% (at 50 mg). Alerting effects were observed starting at 67% occupancy (approximately 5 mg dose), with difficulty getting to sleep beginning at the 5 mg dose (72% occupancy). [1] In a phase 1 study, sleep disturbances (insomnia) were reported as adverse events after multiple dosing. [1] |
| Animal Protocol |
Animal/Disease Models: SD rats[1]
Doses: 3, 10 and 30 mg/kg Route of Administration: Oral administration, once Experimental Results: demonstrated a statistically significant increase in tele-methylhistamine levels at 30 mg/kg. Animal/Disease Models: P-gp-deficient mdr1a (-/-) and wild type mdr1a (+/+) CF-1 mice[1] Doses: 10 mg/kg Route of Administration: Oral administration, once Experimental Results: The brain-to-plasma ratio in mdr1a (-/-) mice (b/p = 14) was remarkably higher than that in SD rats (b/p = 1.1) and mdr1a (+/ +) mice (b/p = 0.8). Animal/Disease Models: Male SD (Sprague-Dawley) rats, male Beagle dogs, and male rhesus monkeys[1] Doses: 1 or 3 mg/kg Route of Administration: IV or PO (pharmacokinetic/PK Analysis) Experimental Results: pharmacokinetic/PK Parameters of 1 in Rats, Dogs, and Rhesus Monkeysa[1] No animal protocols described for MK-0249 in this review. Clinical protocols: In a phase 2 schizophrenia trial, patients received 10 mg once daily for 4 weeks. [1] In PET occupancy studies, healthy volunteers received single oral doses of MK-0249 at 2.5, 5, 10, 25, and 50 mg. [1] |
| ADME/Pharmacokinetics |
No detailed ADME/pharmacokinetic parameters provided for MK-0249 in this review. The half-life (t1/2) is listed as N.A. (not available) in Table 2. [1]
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| Toxicity/Toxicokinetics |
Difficulty getting to sleep (insomnia) was reported as a common side effect, starting at the 5 mg dose (72% receptor occupancy). Sleep disturbances were noted in phase 1 multiple-dose studies. [1]
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| References | |
| Additional Infomation |
MK0249 has been used in trials to study the treatment of hypoventilation syndrome, Alzheimer's disease, paranoid schizophrenia, obstructive sleep apnea, and excessive daytime sleepiness.
MK-0249 is one of several H3 receptor antagonists that advanced to clinical trials. Its chemical structure has not been disclosed. The compound was evaluated in phase 2 trials for adult ADHD, Alzheimer's disease, and schizophrenia. A phase 2 trial for daytime sleepiness in sleep apnea was terminated. It showed alerting effects at 67% receptor occupancy, but no efficacy in schizophrenic patients at 10 mg (achieving >85% occupancy). [1] |
| Molecular Formula |
C23H24F3N3O2
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|---|---|
| Molecular Weight |
431.450776100159
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| Exact Mass |
431.182
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| CAS # |
1167574-41-5
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| Related CAS # |
862309-06-6;
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| PubChem CID |
11697697
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.515
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
31
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| Complexity |
655
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NC2=CC=CC(=C2C(=O)N1C3=CC=C(C=C3)OCCCN4CCCC4)C(F)(F)F
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| InChi Key |
DDDZBLNULGDPGA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H24F3N3O2/c1-16-27-20-7-4-6-19(23(24,25)26)21(20)22(30)29(16)17-8-10-18(11-9-17)31-15-5-14-28-12-2-3-13-28/h4,6-11H,2-3,5,12-15H2,1H3
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| Chemical Name |
2-methyl-3-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl)-5-(trifluoromethyl)quinazolin-4(3H)-one
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| Synonyms |
MK-0249; MK0249; MK 0249
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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 | 2.3178 mL | 11.5888 mL | 23.1777 mL | |
| 5 mM | 0.4636 mL | 2.3178 mL | 4.6355 mL | |
| 10 mM | 0.2318 mL | 1.1589 mL | 2.3178 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.
Link: https://clinicaltrials.gov/ct2/show/NCT00874939
Conditions:Alzheimer's Disease|DementiaLink: https://clinicaltrials.gov/ct2/show/NCT00506077
Conditions:Paranoid SchizophreniaLink: https://clinicaltrials.gov/ct2/show/NCT00475735
Conditions:Attention-Deficit/Hyperactivity Disorder (ADHD)
Title:MK0249 for the Symptomatic Treatment of Alzheimer's Disease (MK0249-011)
Status:Completed
updateDate:2015-02-12
Ctid:NCT00420420
Link: https://clinicaltrials.gov/ct2/show/NCT00420420
Conditions:Alzheimer's DiseaseProducts are for research use only; We do not sell to patients
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