5-HT_1B Receptor ( pEC50 = 8.2 ); 5-HT_1D Receptor
It is thought that neurogenic inflammation and cerebral vasodilatation are key players in the pathophysiology of migraine. While 5-HT1D activation inhibits neurogenic inflammation, 5-HT1B activation reverses cerebral vasodilatation. While frovatriptan has a moderate affinity for the subtypes of 5-HT1A and 5-HT1F receptors, it has a high affinity for 5-HT1B and 5-HT1D receptors. Frovatriptan exhibits a moderate affinity for the 5-HT7 receptors, a property linked to the relaxation of the coronary arteries in dogs[1].

It is thought that neurogenic inflammation and cerebral vasodilatation are key players in the pathophysiology of migraine. While 5-HT1D activation inhibits neurogenic inflammation, 5-HT1B activation reverses cerebral vasodilatation. While frovatriptan has a moderate affinity for the subtypes of 5-HT1A and 5-HT1F receptors, it has a high affinity for 5-HT1B and 5-HT1D receptors. Frovatriptan exhibits a moderate affinity for the 5-HT7 receptors, a property linked to the relaxation of the coronary arteries in dogs[1].

Frovatriptan has an oral bioavailability of 22%–30%, which is unaffected by meals. 60%–70% of the plasma's maximum concentration is reached in an hour, even though it takes two to three hours to reach its maximum. A steady state is achieved in 4-5 days. The binding of plasma proteins is only 15%. The relative terminal long half-life of roughly 26 hours is the most distinctive feature. Since frovatriptan is primarily metabolized by CYP1A2 and excreted by the kidney and liver, mild failure of either organ should not be a treatment-limiting factor[1].
Frovatriptan (0.1, 0.2, and 0.3 mg/kg; a single bolus intraduodenal administration) treatment bolus intraduodenal administration) increases carotid vascular resistance, which lasts for at least five hours in dogs[2].

The oral bioavailability of fluvatriptan succinate is 22%–30%, unaffected by food [1]. Peak plasma concentration (Cmax) is reached in 2–3 hours, and 60%–70% of Cmax can be reached within 1 hour [1]. Steady-state plasma concentrations are reached in 4–5 days [1]. Plasma protein binding is low, at 15% [1]. The terminal half-life is approximately 26 hours, significantly longer than other triptans (3–6 hours) [1]. Fluvatriptan is primarily metabolized by the cytochrome P450 enzyme CYP1A2 [1]. It is cleared by the kidneys and liver, and its use is not limited by mild renal or hepatic failure [1]. Fluvatriptan has a low risk. Drug interactions [1]

The adverse reaction profile of 2.5 mg fluvatriptan is comparable to that of 100 mg sumatriptan, and in some cases even lower. The specific incidence rates (%) of adverse reactions for fluvatriptan and sumatriptan are as follows: dizziness 5.2% vs 5.8%; headache 3.8% vs 4.6%; nausea 3.8% vs 7.9%; fatigue 3.3% vs 6.0%; paresthesia 2.7% vs 5.4%; flushing 2.3% vs 1.0%; temperature sensation changes 2.1% vs 3.3%; abdominal pain 1.9% vs 3.5%; dry mouth 1.5% vs 2.3%; bone pain 1.5% vs 3.7%; chest pain 1.3% vs 2.9%; drowsiness 1.0% vs 2.7%; vomiting 0.6% vs 2.5%. The incidence of fatigue was 0.4 vs 2.3[1]
In this study, the overall incidence of adverse events was 36% for fluvatriptan and 43% for sumatriptan, similar to placebo[1]
Fluvatriptan is contraindicated in patients with ischemic heart disease, coronary artery spasm, cerebrovascular or peripheral vascular disease, severe renal or hepatic impairment, hemiplegic or basilar artery migraine, and pregnant and lactating women[1]
A study in patients with coronary artery disease or high-risk populations showed no difference in the incidence of adverse events between fluvatriptan and placebo[1]

[1]. 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.

Fluvatriptan succinate is the succinate form of fluvatriptan, a synthetic triptan drug with serotonin (5-HT) receptor agonist activity. Fluvatriptan succinate selectively and with high affinity binds to 5-HT1B and presynaptic 5-HT1D receptors in extracerebral and intracranial arteries. This results in inhibition of serotonin activity, causing vasoconstriction of the painfully dilated blood vessels during a migraine attack. Fluvatriptan succinate is indicated for the acute treatment of migraine. (NCI05)
See also: fulvatriptan (containing the active ingredient).

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Frotriptan is a triptan used to treat acute migraine with or without aura in adults[1]
Its mechanism of action is thought to be selective constriction of extracranial and intracranial blood vessels, inhibition of the trigeminal nerve endings innervating these vessels, and potential inhibition of central neurons in the trigeminal caudate nucleus[1]
In three randomized, placebo-controlled trials involving 2,676 migraine patients, a single oral dose of 2.5 mg frovatriptan resulted in headache relief (reduction from severe/moderate pain to mild/no pain) in 37%–46% of patients within 2 hours, compared to only 21%–27% in the placebo group. After 4 hours, the response rate was 56%–65%, compared to 31%–38% in the placebo group[1]
After 2 hours, the pain-free rate was 9%–14% in the frovatriptan group, compared to 2%–3% in the placebo group. Four hours later, the pain-free rates were 27%–32% and 9%–14% (placebo group), respectively [1]. Fluvatriptan was significantly superior to placebo in relieving related symptoms such as nausea, photophobia, and phonophobia [1]. The headache recurrence rate within 24 hours after initial relief was low (10%–25%) and consistently lower than that in the placebo group (24%–31%) [1]. The 24-hour sustained relief rate (4-hour relief without recurrence) was 47%–51% (fluvatriptan group) and 22%–27% (placebo group), respectively [1].
Its long half-life and potent 5-HT1B receptor agonism make it particularly suitable for the treatment of long-lasting migraines, recurrent migraines, and short-term (micro-dose) prevention, such as in menstrual-related migraines (MRM) [1]
A study of women with MRM showed that taking frovatriptan (2.5 mg once or twice daily for 6 days, starting 2 days before the expected headache onset) before and after menstruation effectively reduced the incidence, severity, and duration of MRM attacks and reduced the need for emergency medication [1]
Based on its pharmacokinetic characteristics, the authors suggest that potential off-label uses for frovatriptan include: short-term prevention against predictable triggers (e.g., travel, stress), treatment during the aura phase, and providing sustained relief in cluster headaches until preventative medication takes effect [1]

C18H23N3O5

361.39

361.164

C, 56.98; H, 6.64; N, 11.08; O, 25.30

158930-09-7

Frovatriptan succinate hydrate; 158930-17-7; Frovatriptan; 158747-02-5; Frovatriptan-d3 succinate

152944

Solid powder

515.2ºC at 760 mmHg

265.4ºC

1.01E-10mmHg at 25°C

2.554

5

6

5

26

426

1

CN[C@@H]1CCC2=C(C3C=C(C(=O)N)C=CC=3N2)C1.OC(CCC(=O)O)=O

WHTHWNUUXINXHN-SBSPUUFOSA-N

InChI=1S/C14H17N3O.C4H6O4/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)/t9-;/m1./s1

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)