Absorption, Distribution and Excretion
Absorbed well (oral bioavailability 74%), rapidly, reaching peak plasma concentrations in 2-5 hours. Absorption is slowed during migraine attacks. 170 L 6.6 mL/min/kg Metabolism/Metabolites Primarily metabolized in the liver. In vitro studies have shown that naratriptan can be metabolized into various inactive metabolites by multiple cytochrome P450 isoenzymes. Primarily metabolized in the liver. In vitro studies have shown that naratriptan can be metabolized into various inactive metabolites by multiple cytochrome P450 isoenzymes. Half-life: 5-8 hours Biological half-life 5-8 hours

Toxicity Summary
Triptans' anti-migraine effects involve three distinct pharmacological actions: (1) stimulation of presynaptic 5-HT1D receptors, thereby inhibiting dural vasodilation and inflammation; (2) direct inhibition of trigeminal nucleus cell excitability by stimulating 5-HT1B/1D receptors in the brainstem; and (3) vasoconstriction of the meninges, dura mater, cerebral vessels, or pia mater due to stimulating 5-HT1B receptors in blood vessels.

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Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Published experience regarding the use of naratriptan during lactation is limited. If a mother of an older infant requires naratriptan, this is not a reason to discontinue breastfeeding, but alternative medications should be considered until more data are available, especially when breastfeeding newborns or premature infants. Nipple pain, burning sensation, and breast pain have been reported after taking sumatriptan and other triptans. This is sometimes accompanied by reduced milk production.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
A review of four European adverse reaction databases found 26 reports of nipple pain, burning sensation, breast pain, breast engorgement, and/or painful milk ejection in breastfeeding women taking triptans. The pain was sometimes severe and occasionally led to a decrease in milk production. The pain usually subsided gradually as the drug was metabolized. The authors suggest that triptans may cause vasoconstriction in the arteries surrounding the breast, nipple, mammary alveoli, and milk ducts, thereby causing pain and painful milk ejection reflex.

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Protein binding rate
28%-31% (concentration range 50 to 1000 ng/mL)

Naratriptan is a sulfonamide drug belonging to the tryptamine and heteroarylpiperidine classes. It is a serotonergic agonist and vasoconstrictor. Naratriptan is a triptan drug selective for serotonin 1 receptor subtypes. It is commonly used to treat migraines. Naratriptan is a serotonin 1b and serotonin 1d receptor agonist. Its mechanism of action is as a serotonin 1b and serotonin 1d receptor agonist. Naratriptan has only been found in individuals who have used or taken this drug. It is a triptan drug used to treat migraines. It is a selective serotonin 1 receptor subtype agonist. Triptans have three distinct pharmacological effects in treating migraines: (1) stimulation of presynaptic 5-HT1D receptors, thereby inhibiting dural vasodilation and inflammation; (2) direct inhibition of trigeminal nucleus cell excitability through 5-HT1B/1D receptor agonism in the brainstem; and (3) vasoconstriction of the meninges, dura mater, cerebral vessels, or pia mater due to vasoconstriction of vascular 5-HT1B receptors. See also: Naratriptan hydrochloride (salt form).
Indications
For the treatment of acute migraine attacks in adults with or without aura.
FDA Label

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Mechanism of Action
The anti-migraine effects of triptans involve three distinct pharmacological actions: (1) stimulation of presynaptic 5-HT1D receptors, thereby inhibiting dural vasodilation and inflammation; (2) direct inhibition of trigeminal nucleus cell excitability via 5-HT1B/1D receptor agonism in the brainstem; and (3) vasoconstriction of the meninges, dura mater, cerebral vessels, or pia mater due to vascular 5-HT1B receptor agonism.

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Pharmacodynamics
Naratriptan is a selective serotonin (5-hydroxytryptamine; 5-HT) 1B and 1D receptor agonist. Its structural and pharmacological properties are similar to those of other selective 5-HT1B/1D receptor agonists. Naratriptan exhibits weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors, and shows no significant affinity or pharmacological activity for 5-HT2, 5-HT3, or 5-HT4 receptor subtypes, as well as α1, α2, or β-adrenergic receptors, dopamine 1 receptors, dopamine 2 receptors, muscarinic receptors, or benzodiazepine receptors. This effect is associated with migraine relief in humans. Animal studies indicate that, in addition to causing vasoconstriction, naratriptan can activate 5-HT1 receptors on the trigeminal nerve endings that innervate intracranial blood vessels, which may be one reason why naratriptan exerts its anti-migraine effect in humans.

C17H16O2

252.30774

335.166

121679-13-8

Naratriptan hydrochloride;143388-64-1;Naratriptan-d3 hydrochloride;1190021-64-7;Naratriptan-d3;1190043-69-6

4440

Typically exists as solid at room temperature

1.2±0.1 g/cm3

541.3±60.0 °C at 760 mmHg

281.2±32.9 °C

0.0±1.4 mmHg at 25°C

1.605

1.35

2

4

5

23

483

0

O=S(CCC1=CC2=C(NC=C2C3CCN(C)CC3)C=C1)(NC)=O

AMKVXSZCKVJAGH-UHFFFAOYSA-N

InChI=1S/C17H25N3O2S/c1-18-23(21,22)10-7-13-3-4-17-15(11-13)16(12-19-17)14-5-8-20(2)9-6-14/h3-4,11-12,14,18-19H,5-10H2,1-2H3

N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide

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)

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

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.)