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| Clinical data | |
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| Trade names | Relpax, others |
| Other names | UK-116044; UK116044 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a603029 |
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| Routes of administration | By mouth |
| Drug class | Serotonin5-HT1B,5-HT1D,5-HT1E, and5-HT1F receptoragonist;Triptan;Antimigraine agent |
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| Pharmacokinetic data | |
| Bioavailability | 50%[2] |
| Metabolism | MainlyCYP3A4[2] |
| Eliminationhalf-life | 4 hours[2] |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.167.337 |
| Chemical and physical data | |
| Formula | C22H26N2O2S |
| Molar mass | 382.52 g·mol−1 |
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Eletriptan, sold under the brand nameRelpax and used in the form of eletriptan hydrobromide, is a second-generationtriptanmedication intended for treatment ofmigraineheadaches.[2][3][4] It is used as anabortive medication, blocking a migraine attack which is already in progress.[2] Eletriptan is marketed and manufactured byPfizer.[2]
Eletriptan is a therapeutic alternative on theWorld Health Organization's List of Essential Medicines.[5]
Eletriptan was approved by the United StatesFood and Drug Administration (FDA) in December 2002, for the acute treatment of migraine with or withoutaura in adults.[6][2] It is available only byprescription in the United States, Canada, and Australia. It is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine.[2] It is available in 20 mg and 40 mg strengths.[2]
Eletriptan is contraindicated in patients with various diseases of the heart and circulatory system, such as angina pectoris, severe hypertension, andheart failure, as well as in patients that have had a stroke or heart attack.[2] This is due to the unusual side effect of coronary vasoconstriction due to serotonin 5-HT1B receptor agonism, which can precipitate aheart attack in those already at risk.[2] It is also contraindicated in severekidney (renal) orliver (hepatic) impairment due to its extensive liver metabolism throughCYP3A4.[7][2]
Common side effects includehypertension,tachycardia, headache, dizziness, drowsiness, and symptoms similar toangina pectoris.[2] Severe allergic reactions have been seen rarely.[7][2]
Strong inhibitors of the liver enzyme CYP3A4, such aserythromycin andketoconazole, significantly increase blood plasma concentration of eletriptan and should be separated by at least 72 hours.[2]Ergot alkaloids, such asdihydroergotamine, add to the drug's hypertensive effect and should be separated by at least 24 hours.[7][2]
| Target | Affinity (Ki, nM) |
|---|---|
| 5-HT1A | 1.9–45 (Ki) 417–1,820 (EC50Tooltip half-maximal effective concentration) |
| 5-HT1B | 0.52–15.1 (Ki) 8.1–60 (EC50) 83% (EmaxTooltip maximal efficacy) |
| 5-HT1D | 0.10–1.5 (Ki) 0.63–0.91 (EC50) |
| 5-HT1E | 40–62 (Ki) 30–126 (EC50) |
| 5-HT1F | 5–20 (Ki) 7.4–132 (EC50) |
| 5-HT2A | 1,150–>3,160 (Ki) 851 (EC50) |
| 5-HT2B | 447 (Ki) 155 (EC50) |
| 5-HT2C | >3,160 (Ki) ND (EC50) |
| 5-HT3 | >3,160 (mouse) |
| 5-HT4 | >3,160 (guinea pig) |
| 5-HT5A | 977–1,584 (rat) |
| 5-HT6 | 525 |
| 5-HT7 | 200 (Ki) 355 (EC50) |
| α1A–α1D | ND |
| α2A–α2C | ND |
| β1–β3 | ND |
| D1–D5 | ND |
| H1–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:[8][9][10][11][12][13][14][15] [16][17][18][19] | |
Eletriptan is believed to reduce swelling of the blood vessels surrounding the brain. This swelling is associated with the head pain of a migraine attack. Eletriptan blocks the release of substances from nerve endings that cause more pain and other symptoms like nausea, and sensitivity to light and sound. It is thought that these actions contribute to relief of symptoms by eletriptan.
Eletriptan is aserotonin receptor agonist, specifically anagonist of certain5-HT1 family receptors.[2] Eletriptan binds with high affinity to the5-HT[1B,1D,1F] receptors. It has a modest affinity to the5-HT[1A,1E,2B,7] receptors, and little to no affinity at the5-HT[2A,2C,3,4,5A,6] receptors.
Eletriptan has no significant affinity or pharmacological activity atadrenergicα1,α2, orβ;dopaminergicD1 orD2;muscarinic; oropioid receptors. Eletriptan could be efficiently co-administered with nitric oxide synthase (NOS's) inhibitors for the treatment of NOS-dependent diseases (US patent US 2007/0254940).
Two theories have been proposed to explain the efficacy of 5-HT1 receptor agonists in migraine. One theory suggests that activation of 5-HT1 receptors located on intracranial blood vessels, including those on the arteriovenous anastomoses, leads to vasoconstriction, which is correlated with the relief of migraine headache. The other hypothesis suggests that activation of 5-HT1 receptors on sensory nerve endings in the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
The drug is also notable in being a weak serotonin5-HT2A receptor agonist (EC50Tooltip half-maximal effective concentration = 851 nM), albeit with about two to three orders of magnitude lower activational potency than at the serotonin 5-HT1B and 5-HT1D receptors.[16]
Eletriptan is atryptamine andpyrrolidinylmethylindolederivative and is a 5-substituted andcyclized tryptamine derivative of thepsychedelic drugdimethyltryptamine (DMT).[20]
The experimentallog P is 3.9 and its predicted log P is 1.78 to 4.1.[21][20][22]
Eletriptan was approved for medical use in the United States in 2002.[2] It was covered byU.S. Patent no. 5545644[6][23] andU.S. Patent no. 6110940;[6][24] both now expired.
Eletriptan is sold in the United States, Canada, Australia, and the United Kingdom under the brand name Relpax,[2][25][1] and in several other countries under the brand name Relert.[citation needed]
In the United States, Relpax is marketed byViatris after Upjohn was spun off from Pfizer.[26][27][28]
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 [...]
