Chemistry:Almotriptan

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Almotriptan, sold under the brand names Axert and Almogran among others, is a triptan medication used in the treatment of heavy migraine headache.[1][2][3][4]

Almotriptan was patented in 1992 and approved for medical use in 2000.[5] It was discovered and developed by Almirall-Prodesfarma.[4]

Medical uses

Almotriptan is prescribed to treat the acute headache phase of migraine attacks with or without aura.[6] Almotriptan is approved in the US for the treatment of migraine in adolescents from 12 to 17 years of age.[7]

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.[8]

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.[8]

Pharmacology

Mechanism of action

Almotriptan activities
Target Affinity (Ki, nM)
5-HT1A 186–850 (Ki)
3,310–>10,000 (EC50)
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 ND
SERT ND
NET ND
DAT ND

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.[8]

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.[9]

Chemistry

Almotriptan is a tryptamine derivative and a 5-substituted derivative of the psychedelic drug dimethyltryptamine (DMT).[10]

Its experimental and predicted log P are both 1.6.[10]

History

Almotriptan was patented in 1992 and was approved for medical use in 2000.[5]

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 in the treatment of migraine". Drugs Today (Barc) 37 (1): 5–21. January 2001. doi:10.1358/dot.2001.37.1.844180. PMID 12783094. 
  2. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named PalaciosRabassedaCastaner1999
  3. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Holm_1999
  4. ↑ 4.0 4.1 "Almotriptan". 5 November 2023. https://adisinsight.springer.com/drugs/800005783. 
  5. ↑ 5.0 5.1 (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 531. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA531. 
  6. ↑ "Almotriptan Facts and Comparisons". Drugs.com. https://www.drugs.com/cdi/almotriptan.html. 
  7. ↑ "Treatment of pediatric migraine in the emergency room". Pediatric Neurology (Elsevier BV) 47 (4): 233–241. October 2012. doi:10.1016/j.pediatrneurol.2012.06.001. PMID 22964436. 
  8. ↑ 8.0 8.1 8.2 "Almotriptan: a review of its use in migraine". Drugs 62 (2): 387–414. 2002. doi:10.2165/00003495-200262020-00010. PMID 11817980. 
  9. ↑ "Clinical pharmacokinetics of almotriptan, a serotonin 5-HT(1B/1D) receptor agonist for the treatment of migraine". Clinical Pharmacokinetics 44 (3): 237–246. 2005. doi:10.2165/00003088-200544030-00002. PMID 15762767. 
  10. ↑ 10.0 10.1 "Almotriptan". https://pubchem.ncbi.nlm.nih.gov/compound/123606. 



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