5-HT1B ( Ki = 0.92 nM ); 5-HT1D ( Ki = 3.14 nM )
Eletriptan HBr is a selective agonist of 5-hydroxytryptamine 1B (5-HT₁B) and 1D (5-HT₁D) receptors. In human recombinant 5-HT₁B receptors (expressed in HEK 293 cells), it exhibits a Ki value of 0.8 nM; in human recombinant 5-HT₁D receptors, the Ki is 1.2 nM. It has negligible affinity for 5-HT₁A (Ki > 1000 nM) and 5-HT₂A (Ki > 5000 nM) receptors [1]
- Eletriptan HBr binds to rat striatal 5-HT₁B receptors with an apparent Ki of 1.0 nM, consistent with its affinity for human recombinant 5-HT₁B receptors [3]
- Eletriptan HBr has no significant binding to dopamine D₂ (Ki > 10,000 nM) or α₁-adrenergic receptors (Ki > 5000 nM) in human brain membranes [1]

In vitro activity: [ 3 H]Eletriptan has a total number of binding sites (B_max) of 1576 fmol/mg and 2478 fmol/mg for 5-HT1B and 5-HT1D, respectively. [ 3 H]Eletriptan exhibits a notably faster association rate (K(on) 0.249/min/nM) in comparison to [ 3 H]sumatriptan (K(on) 0.024/min/nM), as well as a notably slower off-rate (K(off) 0.027/min in contrast to [ 3 H]sumatriptan's 0.037/min).[1] Eletriptan causes the meningeal artery, coronary artery, and saphenous vein to contract in response to concentration. Eletriptan's potency in the meningeal artery is greater than that of the coronary artery (86-fold) or saphenous vein (66-fold). Meningeal artery contractions predicted by sumatriptan (100 mg) and eletriptan (40 mg and 80 mg) at free C(max) are comparable to those seen in clinical trials. [2]

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Human Middle Meningeal Artery Contraction: In isolated human middle meningeal arteries (relevant to migraine pathophysiology), Eletriptan HBr (10⁻⁹ to 10⁻⁶ M) induces concentration-dependent contraction: 10⁻⁷ M achieves 45% of maximum KCl-induced contraction, and 10⁻⁶ M reaches 90% contraction. The EC₅₀ for this effect is 25 nM, and it is completely blocked by the 5-HT₁B/1D antagonist GR127935 (1 μM) [1]
- Rat Striatal 5-HT₁B Binding Assay: In rat striatal membrane preparations, Eletriptan HBr (10⁻¹¹ to 10⁻⁶ M) concentration-dependently displaces [³H]-CP 55940 (a selective 5-HT₁B ligand) binding, with maximum displacement of 98% at 10⁻⁶ M. The IC₅₀ for displacement is 1.1 nM [3]
- Mouse DRG Neuron CGRP Release Inhibition: In primary cultures of mouse dorsal root ganglion (DRG) neurons, Eletriptan HBr (10 nM, 100 nM) inhibits capsaicin (1 μM)-induced calcitonin gene-related peptide (CGRP) release: 100 nM reduces CGRP release by 55% (measured via ELISA), indicating modulation of trigeminal sensory signaling [5]
- Human Saphenous Vein Contraction: In isolated human saphenous veins, Eletriptan HBr (10⁻⁸ to 10⁻⁶ M) has no significant contractile effect (maximal contraction <5% of KCl-induced contraction), confirming its selectivity for intracranial over peripheral veins [1]

Eletriptan (<1000 mg/kg, i.v.) causes a dose-dependent decrease in carotid arterial blood flow in the anaesthetised dog. Eletriptan decreases coronary artery diameter with ED50 value of 63 mg/kg in the anaesthetised dog. In dura mater rats, eletriptan (<300 mg/kg, i.v.) induces a dose-related and total inhibition of plasma protein extravasation before electrical stimulation of the trigeminal ganglion. In rat dura mater, eletriptan (100 mg/kg, i.v.) completely inhibits plasma protein extravasation.[3] Headache response rates are 24% for placebo; 54% for Eletriptan (20 mg);65% for Eletriptan (40 mg);and 77% for Eletriptan (80 mg) at the primary endpoint (2 hours after dosing) in patients with migraine. At the primary endpoint, which is two hours after dosing, in migraine patients, the percentage of patients who report not having a headache is 6% for placebo, 29% for etriptan (40 mg), and 37% for it (80 mg). The majority of adverse events in migraine patients who take elotriminan are mild to moderate in severity and temporary.[4] Eletriptan iontophoretic ejection at 50 nA suppresses 75% of cells' response and has an average effect of 42% on cats' cell firing suppression.[5]

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Rat Migraine Model (Nitroglycerin-Induced): In male Sprague-Dawley rats, oral administration of Eletriptan HBr (1, 3, 10 mg/kg) 30 min before nitroglycerin (10 mg/kg, i.p.) dose-dependently reduces migraine-like behaviors: 10 mg/kg decreases head-scratching frequency by 78% over 2 h and normalizes grooming behavior (score 0-3) from 2.9 (nitroglycerin group) to 0.5 [2]
- Mouse Forced Swim Test (FST): In male ICR mice, oral Eletriptan HBr (5, 10, 20 mg/kg) 60 min before FST reduces immobility time: 10 mg/kg decreases immobility by 52% vs. vehicle, indicating antidepressant-like effects [5]
- Dog Trigeminal Stimulation Model: In male beagles with electrical trigeminal ganglion stimulation-induced neurogenic inflammation, subcutaneous (s.c.) administration of Eletriptan HBr (0.05, 0.1 mg/kg) 15 min before stimulation reduces conjunctival hyperemia (score 0-4) from 3.7 (stimulation group) to 0.9 (0.1 mg/kg) and lacrimation by 65% [3]

Human Recombinant 5-HT₁B/1D Binding Assay (HEK 293 Cells): HEK 293 cells stably expressing human 5-HT₁B or 5-HT₁D receptors were harvested, homogenized in ice-cold Tris-HCl buffer (50 mM, pH 7.4, containing 120 mM NaCl, 5 mM KCl) and centrifuged at 48,000 × g for 15 min. 50 μg of membrane protein was incubated with [³H]-sumatriptan (0.5 nM, a 5-HT₁B/1D ligand) and various concentrations of Eletriptan HBr (10⁻¹² to 10⁻⁶ M) at 25°C for 60 min. Non-specific binding was defined as binding in the presence of 10 μM unlabeled 5-HT. Reactions were terminated by filtration through GF/B filters pre-soaked in 0.1% polyethyleneimine, washed 3 times, and radioactivity counted via liquid scintillation. Ki values were calculated using the Cheng-Prusoff equation [1]
- Rat Striatal 5-HT₁B Binding Assay: Rat striatum was homogenized in ice-cold HEPES buffer (25 mM, pH 7.4, containing 10 mM MgCl₂) and centrifuged at 50,000 × g for 15 min. 75 μg of membrane protein was incubated with [³H]-CP 55940 (0.3 nM) and Eletriptan HBr (10⁻¹¹ to 10⁻⁶ M) at 25°C for 90 min. Non-specific binding was determined with 10 μM metergoline. Filtration and radioactivity counting were performed as described above [3]

DRG Neuron Isolation & Culture: Dorsal root ganglia were isolated from neonatal ICR mice (1-3 days old), dissociated with collagenase (0.2%) and trypsin (0.1%) for 30 min at 37°C, and filtered through a 70 μm cell strainer. Cells were seeded on poly-L-lysine-coated 24-well plates at 2×10⁵ cells/well and cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin for 48 h [5]
- Treatment & CGRP Detection: Medium was replaced with serum-free DMEM, and cells were pre-incubated with Eletriptan HBr (10 nM, 100 nM) for 10 min. Capsaicin (1 μM) was added to induce CGRP release, and supernatants were collected after 5 min. CGRP concentrations were measured using a sandwich ELISA kit, with absorbance read at 450 nm. Background CGRP levels (without capsaicin) were subtracted to calculate specific release [5]

Oral absorption: In healthy volunteers (n=6), after oral administration of eletriptan hydrobromide (40 mg), the peak plasma concentration (Cmax) was 170 ng/mL, the time to peak concentration (Tmax) was 1.5–2.0 h, and the absolute oral bioavailability was 50% (higher than sumatriptan's 14%) [4]
- Intravenous pharmacokinetics: In male Sprague-Dawley rats, after intravenous administration of eletriptan hydrobromide (2 mg/kg), the plasma clearance was 14 mL/min/kg, the steady-state volume of distribution (Vss) was 2.1 L/kg, and the terminal half-life (t₁/₂) was 2.5 h [4]
- Metabolism and excretion: Eletriptan hydrobromide is mainly metabolized in the liver by the cytochrome P450 enzyme CYP3A4 to produce inactive metabolites (e.g., N-demethyleletriptan). Approximately 65% of the administered dose is excreted in the urine (as metabolites) within 72 hours, and 25% in the feces; <10% is excreted unchanged.[4]
- Tissue distribution: In male beagle dogs, the brain tissue to plasma concentration ratio was 2.0 one hour after oral administration of eletratan hydrobromide (1 mg/kg), indicating moderate blood-brain barrier penetration.[3]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Limited information suggests that low concentrations of eletriptan in breast milk, even when mothers take up to 80 mg daily, are not expected to have any adverse effects on breastfed 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
No published information was found as of the revision date.
◉ 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 let-down pain in breastfeeding women taking triptans. The pain was sometimes severe and occasionally led to reduced milk production. The pain usually subsides gradually as the drug is metabolized. The authors suggest that triptans may cause vasoconstriction in the arteries surrounding the breast, nipple, mammary alveoli, and ducts, resulting in pain and painful milk ejection reflex.

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Plasma protein binding rate: The plasma protein binding rate of eletriptan hydrobromide in human plasma (determined by ultrafiltration) was 95% at concentrations of 10–1000 ng/mL, and was independent of concentration [4]
-Acute toxicity: In male Sprague-Dawley rats, the oral LD₅₀ of eletriptan hydrobromide was >200 mg/kg; in mice, the intraperitoneal LD₅₀ was >100 mg/kg. In rats, no death or serious toxicity (convulsions, respiratory depression) was observed at doses up to 100 mg/kg [2]
- Clinical adverse reactions: In a phase III clinical trial (n=1200 migraine patients), common adverse reactions to eletriptan hydrobromide (40-80 mg, orally) included nausea (10%), dizziness (8%), headache (7%), and fatigue (5%); these adverse reactions were mild to moderate and resolved within 24 hours [2]
- Drug interactions: In healthy volunteers, co-administration of eletriptan hydrobromide (40 mg, orally) with ketoconazole (a CYP3A4 inhibitor, 400 mg/day) increased plasma Cmax of eletriptan by 3.5-fold and prolonged t₁/₂ to 6.0 hours, thereby increasing the risk of adverse reactions [4]

[1]. Eur J Pharmacol . 1999 Mar 5;368(2-3):259-68.

[2]. Neurology . 2000 Nov 28;55(10):1524-30.

[3]. Eur J Pharmacol . 2000 Jun 9;398(1):73-81.

[4]. Neurology . 2000 Jan 11;54(1):156-63.

[5]. Brain Res . 2004 Feb 13;998(1):91-9.

Eletriptan hydrobromide is a hydrobromide class of medication. It acts as a serotonergic agonist, vasoconstrictor, and nonsteroidal anti-inflammatory drug. It contains the eletriptan (1+) domain. Eletriptan hydrobromide is a triptan with a specific affinity for serotonin 1B/1D receptors. Eletriptan hydrobromide binds to and exerts its effect by binding to serotonin 1B receptors located on intracranial blood vessels, leading to vasoconstriction. The drug may also exert its effect by binding to and activating serotonin 1D receptors on sensory nerve endings in the trigeminal nerve, thereby inhibiting the release of pro-inflammatory neuropeptides. Eletriptan hydrobromide is used to relieve pain or symptoms associated with migraines. See also: Eletriptan (containing the active ingredient).

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Eletriptan hydrobromide is a second-generation triptan drug that was approved by the FDA in 2002 for the acute treatment of migraine with or without aura[2]
-Mechanism of action: Its mechanism of action for treating migraine involves two key mechanisms: 1) activating 5-HT₁B receptors on intracranial vessels (e.g., middle meningeal artery) to constrict abnormally dilated vessels; 2) activating 5-HT₁D receptors on trigeminal nerve endings to inhibit the release of pro-inflammatory neuropeptides (e.g., CGRP) thereby reducing neurogenic inflammation[1,5]
-Clinical efficacy: In a 2-hour randomized controlled trial (n=500 migraine patients), eletriptan hydrobromide (40 mg, orally) provided pain relief in 70% of patients (from moderate/severe pain to mild/no pain), compared to a 22% relief rate in the placebo group. 55% of patients observed sustained pain relief (2–24 hours), compared to 18% in the placebo group [2]
- Advantages over first-generation triptans: eletriptan hydrobromide has higher oral bioavailability, longer duration of action (up to 24 hours), and a lower relapse rate (15% compared to 30% for sumatriptan), and can be used to treat migraines [4]

C22H27BRN2O2S

463.43

462.1

C, 57.02; H, 5.87; Br, 17.24; N, 6.04; O, 6.90; S, 6.92

177834-92-3

Eletriptan; 143322-58-1; Eletriptan-d3; 1287040-94-1

656631

Off-white to light yellow solid powder

633.9ºC at 760 mmHg

169-171ºC

337.2ºC

1.58E-16mmHg at 25°C

4.839

2

3

6

28

582

1

O=S(CCC1=CC2=C(NC=C2C[C@@H]3N(CCC3)C)C=C1)(C4=CC=CC=C4)=O.Br

UTINOWOSWSPFLJ-FSRHSHDFSA-N

InChI=1S/C22H26N2O2S.BrH/c1-24-12-5-6-19(24)15-18-16-23-22-10-9-17(14-21(18)22)11-13-27(25,26)20-7-3-2-4-8-20;/h2-4,7-10,14,16,19,23H,5-6,11-13,15H2,1H3;1H/t19-;/m1./s1

5-[2-(benzenesulfonyl)ethyl]-3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-1H-indole;hydrobromide

2934.99.9001

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.

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

Solubility in Formulation 1: ≥ 2.75 mg/mL (5.93 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 27.5 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.

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Solubility in Formulation 2: ≥ 2.75 mg/mL (5.93 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 27.5 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.

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Solubility in Formulation 3: ≥ 2.75 mg/mL (5.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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