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| Clinical data | |
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| Trade names | Axert, Almogran |
| Other names | LAS-31416; LAS31416 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a603028 |
| License data | |
| Routes of administration | By mouth |
| Drug class | Serotonin5-HT1B,5-HT1D, and5-HT1F receptoragonist;Triptan;Antimigraine agent |
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| Pharmacokinetic data | |
| Bioavailability | 70% |
| Protein binding | 35% |
| Metabolism | Liver |
| Eliminationhalf-life | 3–4 hours |
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| Chemical and physical data | |
| Formula | C17H25N3O2S |
| Molar mass | 335.47 g·mol−1 |
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Almotriptan, sold under the brand namesAxert andAlmogran among others, is atriptanmedication used in the treatment of heavymigraine headache.[4][5][6][7]
Almotriptan was patented in 1992 and approved for medical use in 2000.[8] It was discovered and developed byAlmirall-Prodesfarma.[7]
Almotriptan is prescribed to treat the acute headache phase of migraine attacks with or withoutaura.[9] Almotriptan is approved in the US for the treatment of migraine in adolescents from 12 to 17 years of age.[10]
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 alleviatesnausea,photophobia andphonophobia linked to migraine attacks. Almotriptan has similar efficacy as a standard dose ofsumatriptan, another triptan drug, and fewer adverse effects.[11]
As with other triptans, almotriptan should not be used in patients with a history, symptoms or signs ofischaemic heart disease (myocardial infarction, angina pectoris, documented silent ischaemia, Prinzmetal's angina) or severehypertension and uncontrolled mild or moderate hypertension.Other contraindications are previouscerebrovascular accident (CVA) ortransient ischaemic attack (TIA),peripheral vascular disease, severe hepatic impairment, concomitant administration ofergotamine, ergotamine derivatives (including methysergide) and other 5-HT1B/D agonists.
Almotriptan has proved to have an adverse effects profile similar toplacebo when used following theSummary of Product Characteristics instructions (see references).
Almotriptan ismetabolized mainly bymonoamine oxidase A (MAO-A) and to lesser extent byCYP3A4 andCYP2D6. Studies of drugs used as preventive against migraine (propranolol andverapamil),antidepressants (moclobemide andfluoxetine) yielded results that showed significant altering of thepharmacokinetics of almotriptan though they were deemed not clinically relevant.[11]
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 186–850 (Ki) 3,310–>10,000 (EC50Tooltip 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 |
| TAAR1Tooltip Trace amine-associated receptor 1 | ND |
| SERTTooltip Serotonin transporter | ND |
| NETTooltip Norepinephrine transporter | ND |
| DATTooltip Dopamine transporter | ND |
| 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 serotonin5-HT1B/1D receptors. Binding of the drug to the receptor leads tovasoconstriction 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]
Almotriptan has linearpharmacokinetics up to the 16-fold standard dose. Itsbiological half-life is 3 hours, and itsbioavailability 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 enzymesMAO-A andCYP3A4 andCYP2D6 oxidation.
Almotriptanclearance 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]
Almotriptan is atryptaminederivative and a 5-substituted derivative of thepsychedelic drugdimethyltryptamine (DMT).[24]
Its experimental and predictedlog P are both 1.6.[24]
Almotriptan waspatented in 1992 and was approved for medical use in 2000.[8]
Brand names includeAxert (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), andAmignul (Spain).
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).
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]
Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]
Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]
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 [...]
