Chemistry:Almotriptan

Short description: Chemical compound

Almotriptan

Clinical data
Trade names	Axert
AHFS/Drugs.com	Monograph
MedlinePlus	a603028
License data	US DailyMed: Almotriptan
Routes of administration	By mouth
ATC code	N02CC05 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only EU: Rx-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	70%
Protein binding	35%
Metabolism	Liver
Elimination half-life	3–4 hours
Identifiers
IUPAC name N,N-dimethyl-2- [5-(pyrrolidin-1-ylsulfonylmethyl)- 1H-indol-3-yl]-ethanamine
CAS Number	154323-57-6 N
PubChem CID	123606
IUPHAR/BPS	7110
DrugBank	DB00918 Y
ChemSpider	110198 Y
UNII	1O4XL5SN61
KEGG	D02824 Y as salt: D02825 Y
ChEBI	CHEBI:520985 Y
ChEMBL	ChEMBL1505 Y
Chemical and physical data
Formula	C17H25N3O2S
Molar mass	335.47 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN(C)CCc2c[nH]c3ccc(CS(=O)(=O)N1CCCC1)cc23
InChI 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 Y Key:WKEMJKQOLOHJLZ-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Almotriptan (trade name Axert and others) is a triptan medication discovered and developed by Almirall for the treatment of heavy migraine headache.

It was patented in 1992 and approved for medical use in 2000.

Medical uses

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

Efficacy

The efficacy and tolerability of almotriptan has been studied in numerous randomised, controlled trials totaling more than 4800 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.

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-HT1_B/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).

Pharmacology

Mechanism of action

Like all triptans, almotriptan has a high and specific affinity for serotonin 5-HT_1B/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.

Pharmacokinetics

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

Interactions

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

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) and Amignul (Spain).

External links

• "Almotriptan". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/rn/154323-57-6. 
• "Almotriptan malate". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/almotriptan%20malate.