Frovatriptan succinate hydrate, the succinate and hydrated form of frovatriptan, is a novel and potent 5-HT1B, HT1D receptor agonist and 5-HT7 receptor agonist. Frovatriptan succinate binds selectively and with high affinity to 5-HT 1B and presynaptic 5-HT 1D receptors in the extracerebral and intracranial arteries. This leads to an inhibition of serotonin activity and results in vasoconstriction of the painfully dilated blood vessels during migraine attack. Frovatriptan succinate is indicated for the acute treatment of migraine.

Physicochemical Properties

Molecular Formula	C18H25N3O6
Molecular Weight	379.40800
Exact Mass	379.174
CAS #	158930-17-7
Related CAS #	Frovatriptan;158747-02-5;Frovatriptan succinate;158930-09-7
PubChem CID	152943
Appearance	White to off-white solid powder
Density	1.27g/cm3
Boiling Point	515.2ºC at 760mmHg
Flash Point	265.4ºC
LogP	2.306
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	27
Complexity	426
Defined Atom Stereocenter Count	1
SMILES	CN[C@@H]1CCC2=C(C1)C3=C(N2)C=CC(=C3)C(=O)N.C(CC(=O)O)C(=O)O.O
InChi Key	CUETXFMONOSVJA-KLQYNRQASA-N
InChi Code	InChI=1S/C14H17N3O.C4H6O4.H2O/c1-16-9-3-5-13-11(7-9)10-6-8(14(15)18)2-4-12(10)17-13;5-3(6)1-2-4(7)8;/h2,4,6,9,16-17H,3,5,7H2,1H3,(H2,15,18);1-2H2,(H,5,6)(H,7,8);1H2/t9-;;/m1../s1
Chemical Name	butanedioic acid;(6R)-6-(methylamino)-6,7,8,9-tetrahydro-5H-carbazole-3-carboxamide;hydrate
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)

Biological Activity

Targets	5-HT1B Receptor:8.2 (pEC50); 5-HT1D Receptor
ln Vitro	Migraine pathophysiology is thought to be primarily driven by neurogenic inflammation and cerebral vasodilatation. Brain vasodilatation is reversed by 5-HT1B activation, while neurogenic inflammation is avoided by 5-HT1D activation. 5-HT1B and 5-HT1D receptors are highly affinified for frovatriptan, whereas 5-HT1A and 5-HT1F receptor subtypes are only moderately affinized for the drug. Dog coronary artery relaxation is linked to frovatriptan's modest affinity for 5-HT7 receptors[1].
ln Vivo	Frovatriptan has an oral bioavailability of 22%–30%, which is unaffected by meals. 60%–70% of the plasma's maximal concentration is reached in an hour, even though it takes two to three hours to reach its maximum. It takes four to five days to reach a stable condition. The binding of plasma proteins is just 15%. The relative terminal long half-life of roughly 26 hours is the most distinctive trait. Since frovatriptan is mostly metabolized by CYP1A2 and excreted by the kidney and liver, mild failure of either organ should not be a treatment-limiting factor[1]. When dogs are treated with frovatriptan (0.1, 0.2, and 0.3 mg/kg; administered as a single bolus intraduodenal injection), their carotid vascular resistance increases and remains elevated for at least five hours[2].
References	[1]. Kelman L. Review of frovatriptan in the treatment of migraine. Neuropsychiatr Dis Treat. 2008 Feb;4(1):49-54. [2]. Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan. Headache. 2002 Apr;42 Suppl 2:S47-53.
Additional Infomation	See also: Frovatriptan (annotation moved to); Frovatriptan Succinate (annotation moved to).

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~263.57 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.59 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 (6.59 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	2.6357 mL	13.1784 mL	26.3567 mL
	5 mM	0.5271 mL	2.6357 mL	5.2713 mL
	10 mM	0.2636 mL	1.3178 mL	2.6357 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.