| 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 |
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| Targets |
5-HT1F Receptor ( Ki = 1.6 nM )
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|---|---|
| ln Vitro |
LY334370 does not exhibit vasoconstrictor effects on human cerebral arteries in vitro, unless it is administered at a dose of 10-5 M, at which point it causes an 8.5±5.7% contraction, which is not statistically significant[1].
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| ln Vivo |
Intravenous LY334370 administration at 3 mg/kg (n = 3) or 10 mg/kg (n = 6) causes an increase in dural blood vessel diameter of 135±6% and 106±11%, respectively, after electrical stimulation; these values do not differ significantly from the corresponding control values. Since dural blood vessel diameter is actually 43±4 arbitrary units before drug injection and 43±4 arbitrary units 15 minutes after injection of LY334370 (10 mg/kg), LY334370 has no effect on dural blood vessel diameter per se[1].
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| Cell Assay |
In this study, human cerebral arteries are used. Segments are prepared as previously described, but briefly they are placed in a buffer solution containing (mM) NaCl 119, NaHCo3 15, KCl 4.6, CaCl2 1.5, NaH2PO4 1.2, MgCl2 1.2, and glucose 5.5. Sections of the vessel, measuring 0.5 mm in diameter and 1 to 2 mm in length, are placed in a tissue bath that is heated to 37°C and contains a buffer solution that has been agitated with 5% CO2 and 95% O2. Four mN of tension is applied to the vessel segments, and they are left to stabilize there for one to one and a half hours. Exposure to 60 mM KCl is used to test the reactivity of vessels. Only if the response is similar to the segment used for LY334370 testing is this repeated twice for each segment. As a percentage of the maximum KC1 response, responses to LY334370 are computed[1].
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| Animal Protocol |
There are 300–400 g male Sprague-Dawley rats used. Intravital microscopy and a video dimension analyzer are used to measure the diameter of a branch of the middle meningeal artery in the intact skull of rats housed in a stereotaxic frame after their skulls have been thinned and exposed through drilling. A bipolar stimulating electrode, positioned on the cranial window surface about 200 μM away from the vessel of interest, is used to induce neurogenic vasodilation. After LY334370 (3 or 10 mg/kg, iv.) is administered five minutes after an electrical stimulation response that produces a control vasodilation is produced, and after another fifteen minutes, the electrical stimulation is repeated. For each response, the mean maximum percentage increase in dural vessel diameter relative to the pre-stimulus baseline is calculated. Analysis of variance is then used to compare the vasodilation responses evoked in the presence or absence of LY334370, and paired t-tests are employed to make these comparisons[1].
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| References | |
| Additional Infomation |
This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10(-5) M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg-1, i.v.) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg-1, i.v.) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized, decerebrate rabbit (up to 3 mg kg-1, i.v.), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetised rats at 3 mg kg-1, i.v. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.[1]
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| Molecular Formula |
C21H22FN3O
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|---|---|
| Molecular Weight |
351.41728
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| Exact Mass |
351.17
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| CAS # |
182563-08-2
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| Related CAS # |
199673-74-0(LY334370 hydrochloride)
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| PubChem CID |
5311258
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| Appearance |
White to off-white solid powder
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| Boiling Point |
504.1ºC at 760 mmHg
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| Flash Point |
258.7ºC
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| LogP |
5.181
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
486
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=CC=C(F)C=C1)NC2=CC3=C(C=C2)NC=C3C4CCN(C)CC4
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| InChi Key |
MDMJLMDBRQXOOI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H22FN3O/c1-25-10-8-14(9-11-25)19-13-23-20-7-6-17(12-18(19)20)24-21(26)15-2-4-16(22)5-3-15/h2-7,12-14,23H,8-11H2,1H3,(H,24,26)
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| Chemical Name |
4-fluoro-N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]benzamide
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| Synonyms |
182563-08-2; LY 334370; 4-fluoro-N-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]benzamide; LY-334370; 5Q7I1WL2UY; CHEMBL101690; 4-Fluoro-N-(3-(1-methylpiperidin-4-yl)-1H-indol-5-yl)benzamide; LY334370
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
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| Solubility (In Vitro) |
DMSO: ≥ 55.5 mg/mL (~157.9 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.11 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 (7.11 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8456 mL | 14.2280 mL | 28.4560 mL | |
| 5 mM | 0.5691 mL | 2.8456 mL | 5.6912 mL | |
| 10 mM | 0.2846 mL | 1.4228 mL | 2.8456 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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