| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
Alniditan dihydrochloride targets the serotonin 5-HT1B and 5-HT1D receptors, which are G protein-coupled receptors that mediate vasoconstriction and inhibition of neurotransmitter release. Activation of 5-HT1B receptors on cerebral blood vessels causes vasoconstriction, which is thought to relieve the vasodilation associated with migraine. Activation of 5-HT1D receptors on trigeminal nerve endings inhibits the release of pro-inflammatory neuropeptides, contributing to the antimigraine effect. Alniditan has IC50 values of 1.7 nM for h5-HT1B and 1.3 nM for h5-HT1D.
|
|---|---|
| ln Vitro |
Although alniditan causes significant contractions in rat basilar arteries at high concentrations of 1 mM, it has no vasoconstrictive impact in vitro [1]. This is most likely due to a mechanism other than 5-HT receptor activation.
In vitro, alniditan is a potent agonist at 5-HT1B and 5-HT1D receptors with IC50 values of 1.7 nM for human 5-HT1B and 1.3 nM for human 5-HT1D in HEK 293 cells. It has Kd values of 0.9 nM for 5-HT1B and 1.2 nM for 5-HT1D. These values indicate high affinity and potency at these receptor subtypes. In cell-based assays, alniditan activates 5-HT1B/1D receptor-mediated signaling, such as the inhibition of forskolin-stimulated cAMP accumulation. Its selectivity for 5-HT1B/1D over other serotonin receptors contributes to its antimigraine effects. |
| ln Vivo |
When given 30 minutes before to stimulation, intraperitoneal treatment of Alniditan (ED50 = 9 μg/kg) dose-dependently decreased [125I]-BSA extravasation in rat meninges. In an in vivo model of neurogenic inflammation, alniditan decreases neurogenic inflammation in a dose-dependent manner [1].
In vivo, alniditan has been investigated as a migraine-abortive agent. It is a potent 5-HT1B/5-HT1D receptor agonist that exhibits antimigraine effects. By activating 5-HT1B receptors on cerebral blood vessels, it causes vasoconstriction, which is thought to relieve the vasodilation associated with migraine. By activating 5-HT1D receptors on trigeminal nerve endings, it inhibits the release of pro-inflammatory neuropeptides. However, specific in vivo efficacy data are limited in the available literature. |
| Enzyme Assay |
Non-cellular in vitro assays for alniditan involve receptor binding studies. A standard protocol uses membrane preparations from cells expressing recombinant human 5-HT1B or 5-HT1D receptors. The membranes are incubated with a radiolabeled ligand, such as [³H]GR125743, and varying concentrations of alniditan. Non-specific binding is determined in the presence of an excess of unlabeled serotonin. After incubation, the reaction is terminated by rapid filtration, and the radioactivity bound to the membranes is measured. The Ki or IC50 values are calculated from the competition curves.
|
| Cell Assay |
Cellular assays for alniditan are performed using cell lines expressing 5-HT1B or 5-HT1D receptors, such as HEK293 cells stably transfected with the receptor. Cells are pre-incubated with alniditan at various concentrations and then stimulated with forskolin to increase cAMP levels. The inhibition of forskolin-stimulated cAMP accumulation is measured using a competitive ELISA or a homogeneous time-resolved fluorescence (HTRF) assay. The EC50 for receptor activation is determined from the concentration-response curve.
|
| Animal Protocol |
In vivo animal studies for alniditan are conducted in rodent models of migraine, such as the dural vasodilation model or the trigeminal nerve stimulation model. However, specific protocols for alniditan are not detailed in the available literature. As a migraine-abortive agent, it would be expected to reduce neurogenic inflammation and vasodilation in these models. The compound's effects on cerebral blood flow and pain behavior would be assessed.
|
| ADME/Pharmacokinetics |
Alniditan dihydrochloride has a molecular formula and weight not specified in the available literature. It is a small molecule with drug-like properties. For in vivo studies, it can be formulated in standard vehicles. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have not been fully reported. However, its potency and selectivity suggest it has favorable properties for CNS penetration.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for alniditan have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling alniditan, including the use of personal protective equipment. No specific toxicity data, such as LD50 values, are available in the provided literature.
|
| References |
[1]. Limmroth V, et al. Effects of alniditan on neurogenic oedema in the rat dura mater and on contraction of rat basilar artery. Eur J Pharmacol. 1999 Oct 8;382(2):103-9.
[2]. Lesage AS, et al. Agonistic properties of alniditan, sumatriptan and dihydroergotamine on human 5-HT1B and 5-HT1D receptors expressed in various mammalian cell lines. Br J Pharmacol. 1998 Apr;123(8):1655-65. |
| Additional Infomation |
Alniditan dihydrochloride is a potent 5-HT1B and 5-HT1D receptor agonist with IC50 values of 1.7 nM for h5-HT1B and 1.3 nM for h5-HT1D. It has Kd values of 0.9 nM for 5-HT1B and 1.2 nM for 5-HT1D. Alniditan is a potent and selective serotonin 5-HT1B/5-HT1D receptor agonist that exhibits antimigraine effects. It has been investigated as a migraine-abortive agent. Alniditan is not a clinically approved drug and has not entered recent clinical trials. Its primary application is in research on migraine pathophysiology and 5-HT receptor pharmacology.
|
| Molecular Formula |
C17H26N4O.2[HCL]
|
|---|---|
| Molecular Weight |
375.33642
|
| Exact Mass |
374.164
|
| CAS # |
155428-00-5
|
| Related CAS # |
Alniditan;152317-89-0
|
| PubChem CID |
9907628
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
24
|
| Complexity |
361
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1CNC(=NC1)NCCCNC[C@H]2CCC3=CC=CC=C3O2.Cl.Cl
|
| InChi Key |
GDNITZYKOOTAFK-QCUBGVIVSA-N
|
| InChi Code |
InChI=1S/C17H26N4O.2ClH/c1-2-6-16-14(5-1)7-8-15(22-16)13-18-9-3-10-19-17-20-11-4-12-21-17;;/h1-2,5-6,15,18H,3-4,7-13H2,(H2,19,20,21);2*1H/t15-;;/m1../s1
|
| Chemical Name |
N-[[(2R)-3,4-dihydro-2H-chromen-2-yl]methyl]-N'-(1,4,5,6-tetrahydropyrimidin-2-yl)propane-1,3-diamine;dihydrochloride
|
| 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 Note: Please store this product in a sealed and protected environment, 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)
|
| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~166.52 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.54 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 20.8 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: ≥ 2.08 mg/mL (5.54 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 20.8 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: ≥ 2.08 mg/mL (5.54 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 | 2.6643 mL | 13.3213 mL | 26.6425 mL | |
| 5 mM | 0.5329 mL | 2.6643 mL | 5.3285 mL | |
| 10 mM | 0.2664 mL | 1.3321 mL | 2.6643 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
