5-HT_1B Receptor; 5-HT_1d Receptor
5-HT₁B receptor (Ki: 1.2 nM in human recombinant receptors, Ki: 1.5 nM in bovine caudate membranes), 5-HT₁D receptor (Ki: 0.8 nM in human recombinant receptors, Ki: 1.0 nM in guinea pig cortex membranes); weak binding to 5-HT₁A (Ki > 100 nM), 5-HT₂A (Ki > 200 nM), 5-HT₃ (Ki > 500 nM) receptors [1]

5-HT₁B/₁D receptor binding and activation [1]:
- Human recombinant 5-HT₁B/₁D receptors: Almotriptan Malate competitively displaced [³H]GR125743 (5-HT₁B/₁D ligand) with Ki values of 1.2 nM (5-HT₁B) and 0.8 nM (5-HT₁D). In functional cAMP assays, it dose-dependently inhibited forskolin-induced cAMP accumulation (a hallmark of 5-HT₁B/₁D activation) with EC50 values of 3.5 nM (5-HT₁B) and 2.1 nM (5-HT₁D) [1]
- Bovine caudate membranes (5-HT₁B) and guinea pig cortex membranes (5-HT₁D): Almotriptan Malate showed similar affinity, with Ki values of 1.5 nM and 1.0 nM, respectively; no significant displacement of [³H]ketanserin (5-HT₂A) or [³H]ondansetron (5-HT₃) even at 10 μM [1]
- Vascular smooth muscle contraction [1]:
- Isolated rabbit basilar artery rings: Almotriptan Malate (1 nM–10 μM) induced concentration-dependent contraction, with an EC50 of 10 nM. At 1 μM, it achieved 90% of the maximum contraction induced by 5-HT (10 μM) [1]
- In vitro safety (renal and neuronal cells) [2]:
- Human renal proximal tubule cells: Almotriptan Malate (0.1 μM–100 μM) had no significant effect on cell viability (MTT assay) or lactate dehydrogenase (LDH) release (marker of cell damage) after 24 hours of incubation [2]
- Rat cortical neurons: 100 μM Almotriptan Malate did not alter spontaneous electrical activity (patch-clamp) or glutamate-induced excitotoxicity [2]

Antimigraine activity in animal models [1]:
- Nitroglycerin-induced migraine-like behavior in rats: Subcutaneous administration of Almotriptan Malate at 1 mg/kg, 3 mg/kg, and 10 mg/kg reduced nitroglycerin-induced head scratching (by ~40%, ~65%, ~80%) and facial grooming (by ~35%, ~60%, ~75%) over a 2-hour observation period. The 3 mg/kg dose also normalized nitroglycerin-induced increases in carotid artery blood flow [1]
- Acetylcholine-induced rabbit carotid artery dilation: Intravenous Almotriptan Malate (0.3 mg/kg, 1 mg/kg) reversed acetylcholine-induced dilation by ~50% and ~80%, respectively, indicating intracranial vascular constriction (a key antimigraine mechanism) [1]
- Analgesic activity in mice [1]:
- Tail flick test: Oral Almotriptan Malate (5 mg/kg, 10 mg/kg) increased tail flick latency by ~30% and ~55%, respectively, compared to vehicle control [1]
- In vivo safety (CNS, renal, respiratory) [2]:
- CNS effects in rats: Oral Almotriptan Malate (10 mg/kg, 30 mg/kg, 100 mg/kg) for 28 days had no significant impact on locomotor activity (open field test), rotarod performance (motor coordination), or sedation (sleep latency test). No histopathological changes were observed in the cerebral cortex or cerebellum [2]
- Renal function in dogs: Intravenous Almotriptan Malate (5 mg/kg/day) for 14 days showed no changes in serum creatinine, blood urea nitrogen (BUN), or urinary protein excretion. Renal histology (glomeruli, proximal tubules) was normal [2]
- Respiratory dynamics in cats: Intravenous Almotriptan Malate (0.5 mg/kg, 2 mg/kg) did not alter respiratory rate, tidal volume, or arterial oxygen partial pressure (PaO₂) [2]

5-HT₁B/₁D receptor binding assay [1]:
- Membrane preparation: Bovine caudate (for 5-HT₁B) or guinea pig cortex (for 5-HT₁D) was homogenized in ice-cold Tris-HCl buffer (50 mM, pH 7.4) and centrifuged (12,000×g for 20 minutes). The pellet was resuspended in binding buffer (50 mM Tris-HCl pH 7.4, 10 mM MgCl₂, 0.1% BSA) [1]
- Incubation and detection: Membranes were mixed with [³H]GR125743 (final concentration 0.5 nM) and Almotriptan Malate (0.01 nM–1000 nM) in a total volume of 250 μL. The mixture was incubated at 25°C for 60 minutes, then filtered through glass fiber filters (pre-soaked in 0.1% polyethyleneimine) to separate bound and free ligand. Filters were washed 3 times with ice-cold binding buffer, and radioactivity was measured via liquid scintillation counter. Ki values were calculated using the Cheng-Prusoff equation [1]
- 5-HT₁B/₁D functional assay (cAMP inhibition) [1]:
- HEK293 cells stably expressing human 5-HT₁B or 5-HT₁D receptors were seeded into 24-well plates and cultured for 24 hours. Cells were pre-treated with forskolin (10 μM) for 10 minutes to elevate cAMP, then incubated with Almotriptan Malate (0.1 nM–100 nM) for 30 minutes. Intracellular cAMP was extracted with 0.1 M HCl and quantified via competitive ELISA. EC50 values were derived from dose-response curves of cAMP inhibition [1]

Human renal proximal tubule cell viability assay [2]:
- Cells were seeded into 96-well plates at 5×10³ cells/well and cultured in DMEM/F12 medium (supplemented with 10% FBS, 1% insulin-transferrin-selenium) at 37°C, 5% CO₂. After 24 hours, Almotriptan Malate (0.1 μM–100 μM) was added, and incubation continued for 24 hours. MTT solution (5 mg/mL) was added (20 μL/well) for 4 hours, then supernatant was removed and 150 μL DMSO was added to dissolve formazan. Absorbance at 570 nm was measured, and viability was calculated relative to vehicle control [2]
- Rat cortical neuron electrical activity assay [2]:
- Primary rat cortical neurons (7 days in vitro) were cultured on glass coverslips. Whole-cell patch-clamp recordings were performed using an extracellular solution (140 mM NaCl, 5 mM KCl, 2 mM CaCl₂, 1 mM MgCl₂, 10 mM HEPES) and intracellular solution (130 mM K-gluconate, 10 mM KCl, 10 mM HEPES, 1 mM EGTA). Almotriptan Malate (10 μM, 100 μM) was added to the extracellular solution, and spontaneous action potentials were recorded for 10 minutes to assess neuronal activity [2]

Nitroglycerin-induced migraine rat model [1]:
- Male Sprague-Dawley rats (250–300 g) were randomly divided into 4 groups (n=8/group): vehicle (saline + 0.5% DMSO, subcutaneous), Almotriptan Malate 1 mg/kg, 3 mg/kg, 10 mg/kg (subcutaneous). Thirty minutes later, nitroglycerin (10 mg/kg, subcutaneous) was administered to induce migraine-like behavior. Rats were placed in transparent cages, and head scratching (forepaw to head) and facial grooming (forepaw to face) were recorded every 15 minutes for 2 hours [1]
- Rabbit basilar artery contraction assay [1]:
- Male New Zealand White rabbits (2–2.5 kg) were euthanized, and the basilar artery was dissected into 3 mm rings. Rings were mounted in organ baths containing Krebs-Ringer solution (95% O₂/5% CO₂, 37°C) and connected to force transducers. After equilibration (1 hour, 1 g tension), Almotriptan Malate (1 nM–10 μM) was added cumulatively, and tension changes were recorded. Contraction was expressed as a percentage of the maximum response to 5-HT (10 μM) [1]
- 28-day rat CNS/renal safety study [2]:
- Male Wistar rats (180–220 g) were divided into 4 groups (n=10/group): vehicle (0.5% methylcellulose, oral), Almotriptan Malate 10 mg/kg, 30 mg/kg, 100 mg/kg (oral). Drugs were administered once daily for 28 days. Weekly assessments included: open field test (5 minutes, total distance traveled), rotarod test (5 rpm, time to fall), and sleep latency test (pentobarbital-induced, time to loss of righting reflex). On day 28, blood was collected for serum creatinine/BUN measurement, and brains/kidneys were harvested for histopathological analysis [2]

Rat pharmacokinetics [1]: - Oral administration (10 mg/kg): peak plasma concentration (Cmax) = 250 ng/mL, time to peak concentration (Tmax) = 1.2 h, elimination half-life (t1/2) = 2.8 h, oral bioavailability (F) = 68% [1] - Intravenous administration (2 mg/kg): Cmax = 320 ng/mL, t1/2 = 2.5 h, clearance (CL) = 15 mL/min/kg, volume of distribution (Vd) = 3.5 L/kg [1] - Human pharmacokinetics (Reference 1, clinical data): - Healthy volunteers (n=12) Oral administration (12.5 mg): Cmax = 18 ng/mL, Tmax = 1.5 h, t1/2 = 3.5 h, F = 70% (minimum first-pass metabolism) [1] - Metabolism [1]: - Amotriptan malate is primarily metabolized in the liver via CYP3A4 (approximately 40%) and CYP2D6 (approximately 30%); the major metabolites are inactive (e.g., N-desmethylamotriptan, Ki > 100 nM for 5-HT₁B/₁D) [1] - Excretion [1]: - Approximately 75% of the dose is excreted in the urine within 24 hours (25% as the original drug and 50% as metabolites); approximately 15% is excreted in the feces [1]

Acute toxicity[2]: - Oral LD50 in mice = 2000 mg/kg; oral LD50 in rats = 1800 mg/kg; oral LD50 in dogs = 1500 mg/kg. Acute toxicity symptoms (at a rat dose of 1000 mg/kg) included transient sedation and decreased activity, which were completely resolved within 24 hours[2] - Subacute toxicity (28 days)[2]: - Oral administration of amotriptan malate to rats (10–100 mg/kg/day): No significant changes were observed in body weight, food intake, or hematological parameters (white blood cells, red blood cells, platelets). Serum ALT/AST (liver function) and creatinine/BUN (kidney function) were within the normal range [2] - Intravenous administration of amotratan malate (5 mg/kg/day for 14 days) to dogs: No histopathological lesions were observed in the kidneys, brain or lungs [2] - Plasma protein binding [1]: - 40% in human plasma (balanced dialysis), 38% in rat plasma, and 42% in canine plasma; binding was not concentration-dependent (10–1000 ng/mL) [1] - Drug interactions [2]:

[1]. Pharmacological characterization of almotriptan: an indolic 5-HT receptor agonist for the treatment of migraine. Eur J Pharmacol, 2000. 410(1): p. 33-41.

[2]. Safety profile of almotriptan, a new antimigraine agent. Effects on central nervous system, renal function and respiratory dynamics. Arzneimittelforschung, 2001. 51(9): p. 726-32.

Amotriptan malate is the malate of amotriptan. It is a vasoconstrictor, serotonergic agonist, and nonsteroidal anti-inflammatory drug. It contains amotriptan. Amotriptan malate is the malate of amotriptan, a sulfonamide triptan drug with vasoconstrictive activity. Amotriptan selectively binds to and activates serotonin 5-HT1B and 5-HT1D receptors in the central nervous system (CNS), thereby causing cerebral vasoconstriction. This may help relieve vascular headaches. Amotriptan can also relieve vascular headaches by: preventing the release of vasoactive neuropeptides from the trigeminal axons around the dural vessels during a migraine attack; reducing plasma protein extravasation; and reducing the release of other inflammatory mediators from the trigeminal nerve. See also: Amotriptan (containing the active ingredient). Amotriptan malate (LAS 31416) is a second-generation triptan anti-migraine drug, chemically classified as an indole derivative. It is designed to address the limitations of first-generation triptans (e.g., low oral bioavailability and short half-life) by targeting 5-HT₁B/₁D receptors (key mediators in migraine pathophysiology, such as intracranial vasoconstriction and inhibition of neuropeptide release)[1]. - Mechanism of action for migraine: Amotriptan malate acts as a selective agonist of 5-HT₁B receptors (constricting and dilating intracranial arteries) and 5-HT₁D receptors (inhibiting the release of calcitonin gene-related peptide, CGRP—a migraine-promoting neuropeptide) from trigeminal nerve endings[1]. - Clinical indications: Approved for the acute treatment of migraine with or without aura in adults. The recommended oral dose is 12.5 mg to 25 mg per episode, with a maximum daily dose of 50 mg [1]
- Safety advantages [2]: Amotriptan malate has a good safety profile compared to first-generation triptans (e.g., sumatriptan): low risk of central nervous system side effects (sedation, dizziness), no significant nephrotoxicity, and minimal impact on respiratory function—therefore suitable for patients with mild renal insufficiency or those taking central nervous system medications concurrently [2]

C21H31N3O7S

469.55

469.188

181183-52-8

Almotriptan; 154323-57-6

123607

White to off-white solid powder

1.27g/cm3

538.7ºC at 760mmHg

170-172ºC

279.6ºC

1.13E-11mmHg at 25°C

2.122

4

9

9

32

612

0

S(C([H])([H])C1C([H])=C([H])C2=C(C(=C([H])N2[H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])C=1[H])(N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H])(=O)=O.O([H])C([H])(C(=O)O[H])C([H])([H])C(=O)O[H]

QHATUKWEVNMHRY-UHFFFAOYSA-N

InChI=1S/C17H25N3O2S.C4H6O5/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;5-2(4(8)9)1-3(6)7/h5-6,11-12,18H,3-4,7-10,13H2,1-2H3;2,5H,1H2,(H,6,7)(H,8,9)

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

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: ≥ 2.5 mg/mL (5.32 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 (5.32 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.32 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 50 mg/mL (106.48 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

---

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