Almotriptan

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Almotriptan
Almotriptan skeletal.svg
Almotriptan molecule ball.png
Clinical data
Trade names Axert, Almogran
Other namesLAS-31416; LAS31416
AHFS/Drugs.com Monograph
MedlinePlus a603028
License data
Routes of
administration 		By mouth
Drug class Serotonin 5-HT1B, 5-HT1D, and 5-HT1F receptor agonist; Triptan; Antimigraine agent
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • US: ℞-only [1] [2]
  • EU:Rx-only [3]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 70%
Protein binding 35%
Metabolism Liver
Elimination half-life 3–4 hours
Identifiers
  • N,N-dimethyl-2- [5-(pyrrolidin-1-ylsulfonylmethyl)- 1H-indol-3-yl]-ethanamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C17H25N3O2S
Molar mass 335.47 g·mol−1
3D model (JSmol)
  • CN(C)CCc2c[nH]c3ccc(CS(=O)(=O)N1CCCC1)cc23
  • 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 Yes check.svgY
  • Key:WKEMJKQOLOHJLZ-UHFFFAOYSA-N Yes check.svgY
   (verify)

Almotriptan, sold under the brand names Axert and Almogran among others, is a triptan medication used in the treatment of heavy migraine headache. [4] [5] [6] [7]

Contents

Almotriptan was patented in 1992 and approved for medical use in 2000. [8] It was discovered and developed by Almirall-Prodesfarma. [7]

Medical uses

Almotriptan is prescribed to treat the acute headache phase of migraine attacks with or without aura. [9] Almotriptan is approved in the US for the treatment of migraine in adolescent from 12 to 17 years of age. [10]

Effectiveness

The efficacy and tolerability of almotriptan has been studied in numerous randomized, controlled trials totaling more than 4,800 adults with either moderate or severe attacks of migraine. Its efficacy is significantly more effective than placebo and alleviates nausea, photophobia and phonophobia linked to migraine attacks. Almotriptan has similar efficacy as a standard dose of sumatriptan, another triptan drug, and fewer adverse effects. [11]

Contraindications

As with other triptans, almotriptan should not be used in patients with a history, symptoms or signs of ischaemic heart disease (myocardial infarction, angina pectoris, documented silent ischaemia, Prinzmetal's angina) or severe hypertension and uncontrolled mild or moderate hypertension. Other contraindications are previous cerebrovascular accident (CVA) or transient ischaemic attack (TIA), peripheral vascular disease, severe hepatic impairment, concomitant administration of ergotamine, ergotamine derivatives (including methysergide) and other 5-HT1B/D agonists.

Side effects

Almotriptan has proved to have an adverse effects profile similar to placebo when used following the Summary of Product Characteristics instructions (see references).

Interactions

Almotriptan is metabolized mainly by monoamine oxidase A (MAO-A) and to lesser extent by CYP3A4 and CYP2D6. Studies of drugs used as preventive against migraine (propranolol and verapamil), antidepressants (moclobemide and fluoxetine) yielded results that showed significant altering of the pharmacokinetics of almotriptan though they were deemed not clinically relevant. [11]

Pharmacology

Mechanism of action

Almotriptan activities
Target Affinity (Ki, nM)
5-HT1A 186–850 (Ki)
3,310–>10,000 (EC50 Tooltip half-maximal effective concentration)
5-HT1B 3.5–63 (Ki)
14–100 (EC50)
5-HT1D 5.5–16 (Ki)
18–20 (EC50)
5-HT1E >10,000 (Ki)
>10,000 (EC50)
5-HT1F 23 (Ki)
16–126 (EC50)
5-HT2A >10,000 (Ki)
>10,000 (EC50)
5-HT2B >10,000 (Ki)
6,310 (EC50)
5-HT2C ND (Ki)
ND (EC50)
5-HT3 ND
5-HT4 ND
5-HT5A ND
5-HT6 ND
5-HT7 347 (Ki)
>10,000 (EC50)
α >1,000
α1A–α1D ND
α2A–α2C ND
β >1,000
β1–β3 ND
D1, D2 >1,000
D3–D5 ND
H1 ND
H2 >1,000
H3, H4 ND
M1–M5 ND
I1, I2 ND
σ1, σ2 ND
TAAR1 Tooltip Trace amine-associated receptor 1ND
SERT Tooltip Serotonin transporterND
NET Tooltip Norepinephrine transporterND
DAT Tooltip Dopamine transporterND
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [12] [5] [6] [13] [14] [15] [16]
[4] [17] [18] [19] [20] [21] [22]

Like all triptans, almotriptan has a high and specific affinity for serotonin 5-HT1B/1D receptors. Binding of the drug to the receptor leads to vasoconstriction of the cranial (brain) blood vessels and thus affects the redistribution of blood flow. Almotriptan significantly increases cerebral blood flow and reduces blood flow through extracerebral cranial vessels. Even though it affects cranial blood vessels a single standard dose of almotriptan has no clinically significant effect on blood pressure or heart rate in both young and elderly healthy volunteers. Larger doses seem to slightly increase blood pressure but not beyond clinical relevance. [11]

Pharmacokinetics

Almotriptan has linear pharmacokinetics up to the 16-fold standard dose. Its biological half-life is 3 hours, and its bioavailability 70%.

Cmax is observed 1.5–4 hours after oral administration, and approximately 50% of the drug is excreted unchanged in the urine. Metabolism is mediated through the enzymes MAO-A and CYP3A4 and CYP2D6 oxidation.

Almotriptan clearance is moderately reduced in the elderly but does not require dose adjustment. Sex does not alter the pharmacokinetics of the drug. People with moderate-to-severe renal dysfunction are recommended to use only half the dose. [23]

Chemistry

Almotriptan is a tryptamine derivative and a 5-substituted derivative of the psychedelic drug dimethyltryptamine (DMT). [24]

Its experimental and predicted log P are both 1.6. [24]

History

Almotriptan was patented in 1992 and was approved for medical use in 2000. [8]

Society and culture

Brand names

Brand names include Axert (US, Canada), Almogran (Belgium, Denmark, Finland, France, Germany, Italy, Ireland Portugal, Spain, the United Kingdom, the Netherlands, Sweden, Switzerland, South Korea...), Almotrex (Italy), Almozen (Bulgaria and Poland), Dezamigren (Poland), and Amignul (Spain).

References

  1. ↑ "Almotriptan tablet, film coated". DailyMed. Retrieved 17 February 2021.
  2. ↑ "Axert- almotriptan malate tablet, coated". DailyMed. Retrieved 17 February 2021.
  3. ↑ "Active substance: almotriptan" (PDF). List of nationally authorised medicinal products. Europeans Medicines Agency. 11 February 2021.
  4. 1 2 Rabasseda X (January 2001). "Almotriptan in the treatment of migraine". Drugs Today (Barc). 37 (1): 5–21. doi:10.1358/dot.2001.37.1.844180. PMID   12783094.
  5. 1 2 Palacios, J.M., Rabasseda, X., Castaner, J. (1999). "Almotriptan". Drugs of the Future. 24 (4): 0367. doi:10.1358/dof.1999.024.04.482252 . Retrieved 28 July 2025. Almotriptan is a selective 5-HT1B/1D receptor agonist which shows high and specific affinity for 5-HT1B/1D receptors in cranial vessels, but poor affinity for receptors in peripheral arteries. Affinity for 5-HT1A and 5-HT7 receptors was 35-51 times lower than for 5-HT1B/1D receptors, while affinity for most nonserotonergic receptors was negligible (Ki >1 µM) (6).
  6. 1 2 Holm KJ, Spencer CM (1999). "Almotriptan:". CNS Drugs. 11 (2): 159–164. doi:10.2165/00023210-199911020-00006. ISSN   1172-7047 . Retrieved 28 July 2025. Receptor Binding: Almotriptan has equipotent and selective affinity for 5-HT1B and 5-HT1D receptors.[5] The drug shows a 35- to 51-fold higher affinity for 5-HT1B/1D receptors than other serotonin receptor subtypes (5- HT1A and 5-HT7). It has negligible affinity [inhibition constant (Ki ) >1000 nmol/L] for most relevant receptors that are not specific for serotonin, including the histamine H2 receptor, α-adrenoceptor, βadrenoceptor and dopamine D1 and D2 receptors.[6]
  7. 1 2 "Almotriptan". AdisInsight. 5 November 2023. Retrieved 28 July 2025.
  8. 1 2 Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 531. ISBN   9783527607495.
  9. ↑ "Almotriptan Facts and Comparisons". Drugs.com. Retrieved 7 October 2012.
  10. ↑ Gelfand AA, Goadsby PJ (October 2012). "Treatment of pediatric migraine in the emergency room". Pediatric Neurology. 47 (4). Elsevier BV: 233–241. doi:10.1016/j.pediatrneurol.2012.06.001. PMC   3681416 . PMID   22964436.
  11. 1 2 3 Keam SJ, Goa KL, Figgitt DP (2002). "Almotriptan: a review of its use in migraine". Drugs. 62 (2): 387–414. doi:10.2165/00003495-200262020-00010. PMID   11817980. S2CID   242752549.
  12. ↑ Bou, J., Domenech, T., Gras, J., Beleta, J., Llenas, J., Fernandez, A. G., & Palacios, J. M. (1997). Pharmacological profile of almotriptan, a novel antimigraine agent. Cephalalgia, 17(3), 421-422. https://scholar.google.com/scholar?cluster=1949029248990535503
  13. ↑ De Vries P, Villalón CM, Saxena PR (1999). "Pharmacology of triptans". Emerging Drugs. 4 (1): 107–125. doi:10.1517/14728214.4.1.107. ISSN   1361-9195.
  14. ↑ Tfelt-Hansen P, De Vries P, Saxena PR (December 2000). "Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy". Drugs. 60 (6): 1259–1287. doi:10.2165/00003495-200060060-00003. PMID   11152011.
  15. ↑ Deleu D, Hanssens Y (July 2000). "Current and emerging second-generation triptans in acute migraine therapy: a comparative review". J Clin Pharmacol. 40 (7): 687–700. doi:10.1177/00912700022009431. PMID   10883409.
  16. ↑ Saxena PR, Tfelt-Hansen P (2001). "Success and failure of triptans". The Journal of Headache and Pain. 2 (1): 3–11. doi: 10.1007/s101940170040 . ISSN   1129-2369. PMC   3611827 .
  17. ↑ van den Brink M (22 December 1999). "Coronary Side Effects of Antimigraine Drugs From Patient to Receptor". RePub, Erasmus University Repository. Retrieved 19 June 2025. Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]
  18. ↑ van den Broek RW (13 March 2002). "Vascular Effects of Antimigraine Drugs: pharmacology of human in vitro models in migraine". RePub, Erasmus University Repository. Retrieved 19 June 2025. Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]
  19. ↑ Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJ, Zanelli E, et al. (December 2019). "Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan". British Journal of Pharmacology. 176 (24): 4681–4695. doi:10.1111/bph.14832. PMC   6965684 . PMID   31418454. TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]
  20. ↑ Reuter U, Neeb L (2012). "Lasmiditan hydrochloride". Drugs of the Future. 37 (10): 709. doi:10.1358/dof.2012.037.010.1873629. ISSN   0377-8282 . Retrieved 19 June 2025.
  21. ↑ Mitsikostas DD, Ward TN (2024). "Evidence-based symptomatic treatment of migraine". Migraine Management. Handbook of Clinical Neurology. Vol. 199. pp. 203–218. doi:10.1016/B978-0-12-823357-3.00004-5. ISBN   978-0-12-823357-3. PMID   38307647.
  22. ↑ Comer MB (April 2002). "Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan". Headache. 42 (Suppl 2): S47 –S53. doi:10.1046/j.1526-4610.42.s2.2.x. PMID   12028320.
  23. ↑ McEnroe JD, Fleishaker JC (2005). "Clinical pharmacokinetics of almotriptan, a serotonin 5-HT(1B/1D) receptor agonist for the treatment of migraine". Clinical Pharmacokinetics. 44 (3): 237–246. doi:10.2165/00003088-200544030-00002. PMID   15762767. S2CID   23136754.
  24. 1 2 "Almotriptan". PubChem. Retrieved 29 July 2025.
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