Absorption, Distribution and Excretion
Amotriptan is primarily eliminated by renal excretion (approximately 75% of the oral dose), with about 40% of the administered dose excreted unchanged in the urine. Approximately 13% of the administered dose is excreted in feces, including the original drug and metabolites. Resolution: 180 to 200 liters Resolution: 57 liters/hour [healthy] Resolution: 34.2 liters/hour [moderate renal impairment (creatinine clearance between 31 and 71 mL/min)] Resolution: 9.8 liters/hour [severe renal impairment (creatinine clearance between 10 and 30 mL/min)] Metabolism/Metabolites Known metabolites of amotriptan include methyl(2-{5-[(pyrrolidine-1-sulfonyl)methyl]-1H-indol-3-yl}ethyl)amine and 2-hydroxyamotriptan. Hepatic metabolism Elimination pathway: Amotriptan is primarily excreted via the kidneys (approximately 75% of the oral dose), with about 40% excreted via other routes. The administered dose is excreted unchanged in the urine. Approximately 13% of the administered dose is excreted in the feces, including both the unchanged form and metabolites. Half-life: 3-4 hours.

Toxicity Summary
Amotriptan binds with high affinity to human 5-HT1B and 5-HT1D receptors, leading to intracranial vasoconstriction. Effects During Pregnancy and Lactation ◉ Overview of Use During Lactation Limited published experience regarding the use of amotriptan during lactation, although the dose in breast milk appears to be low. If a mother of an older infant needs to take amotriptan, this is not a reason to stop breastfeeding, but it is best to choose an alternative medication until more data are available, especially when breastfeeding a newborn or premature infant. Nipple pain, burning sensation, and breast pain have been reported after taking sumatriptan and other triptans. Sometimes, taking triptans can lead to reduced milk production. ◉ Effects on Breastfed Infants No published information was found as of the revision date.
◉ Effects on Lactation and Breast Milk
A review of four European adverse reaction databases revealed 26 reports of nipple pain, burning sensation, breast pain, breast engorgement, and/or let-down reflex in breastfeeding women taking triptans. The pain was sometimes severe and occasionally led to reduced 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 ducts, thereby causing pain and the let-down reflex.

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Protein Binding Rate
35%

Amotriptan is an indole compound with a 2-(dimethylamino)ethyl group at the 3-position and a (pyrrolidine-1-ylsulfonyl)methyl group at the 5-position. It is a nonsteroidal anti-inflammatory drug, a serotonin receptor agonist, and a vasoconstrictor. It belongs to the indole, sulfonamide, and tertiary amine classes of compounds. Amotriptan is a triptan used to treat migraines. It belongs to the class of selective serotonin receptor agonists. Its mechanism of action is to constrict cerebral blood vessels, preventing pain signals from reaching the brain and inhibiting the release of certain natural substances that cause pain, nausea, and other migraine symptoms. Amotriptan does not prevent migraine attacks. Amotriptan is a serotonin-1b and serotonin-1d receptor agonist. Its mechanism of action is as a serotonin-1b and serotonin-1d receptor agonist. Amotriptan is a sulfonamide triptan with extracranial and intracranial vasoconstrictive activity. Amotriptan selectively binds to and activates 5-HT1B and 1D receptors in the central nervous system (CNS), causing vasoconstriction both extracerebral and intracranial. This may help relieve vascular headaches. Amotriptan can also relieve vascular headaches by inhibiting the release of vasoactive neuropeptides from trigeminal nerve axons around the dura mater during migraine attacks; reducing plasma protein extravasation; and reducing the release of other inflammatory mediators from the trigeminal nerve. Amotriptan is a triptan used to treat migraines. Amotriptan belongs to the class of selective serotonin receptor agonists. Its mechanism of action is through vasoconstriction in the brain, preventing pain signals from reaching the brain and inhibiting the release of certain natural substances that cause pain, nausea, and other migraine symptoms. Amotriptan does not prevent migraine attacks. See also: Amotriptan malate (in saline form). Drug Indications For the treatment of acute migraines in adults.
FDA Label

Mechanism of Action

Amotriptan has a high affinity for human 5-HT1B and 5-HT1D receptors, leading to intracranial vasoconstriction.
Pharmacodynamics

Amotriptan is a selective serotonin receptor subtype agonist indicated for the treatment of acute migraine attacks in adults with or without aura. Amotriptan is not indicated for the prophylactic treatment of migraine, nor for the treatment of hemiplegic or basilar artery migraine.
Amotriptan is an agonist of vasomotor serotonin receptor subtypes (possibly members of the 5-HT1D family), exhibiting weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors, and 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. In humans, this effect is associated with migraine relief. In addition to causing vasoconstriction, animal studies indicate that amotriptan can also activate 5-HT1 receptors on the trigeminal nerve endings innervating intracranial blood vessels, which may be one reason for its anti-migraine effect in humans.

C17H25N3O2S

335.46

335.166

154323-57-6

Almotriptan malate;181183-52-8

123606

White to off-white solid powder

1.3±0.1 g/cm3

538.7±60.0 °C at 760 mmHg

279.6±32.9 °C

0.0±1.4 mmHg at 25°C

1.634

1.88

1

4

6

23

483

0

CN(C)CCC1=CNC2=C1C=C(C=C2)CS(=O)(=O)N3CCCC3

WKEMJKQOLOHJLZ-UHFFFAOYSA-N

InChI=1S/C17H25N3O2S/c1-19(2)10-7-15-12-18-17-6-5-14(11-16(15)17)13-23(21,22)20-8-3-4-9-20/h5-6,11-12,18H,3-4,7-10,13H2,1-2H3

N,N-dimethyl-2-[5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indol-3-yl]ethanamine

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.)