Eletriptan

Eletriptan

Clinical data
Trade names	Relpax
AHFS/Drugs.com	Monograph
MedlinePlus	a603029
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	oral
ATC code	N02CC06 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	50%
Metabolism	CYP3A4
Biological half-life	4 hours
Identifiers
IUPAC name (R)-3-[(-1-methylpyrrolidin-2-yl)methyl]-5-(2-phenylsulfonylethyl)- 1H-indole
CAS Number	143322-58-1 Y
PubChem CID	77993
IUPHAR/BPS	40
DrugBank	DB00216 Y
ChemSpider	70379 Y
UNII	22QOO9B8KI
KEGG	D01973 N
ChEBI	CHEBI:50922 Y
ChEMBL	CHEMBL1510 Y
ECHA InfoCard	100.167.337
Chemical and physical data
Formula	C22H26N2O2S
Molar mass	382.52 g/mol
3D model (Jmol)	Interactive image
SMILES O=S(=O)(c1ccccc1)CCc4ccc2c(c(cn2)C[C@@H]3N(C)CCC3)c4
InChI InChI=1S/C22H26N2O2S/c1-24-12-5-6-19(24)15-18-16-23-22-10-9-17(14-21(18)22)11-13-27(25,26)20-7-3-2-4-8-20/h2-4,7-10,14,16,19,23H,5-6,11-137T56T N Key:PWVXXGRKLHYWKM-LJQANCHMSA-N Y
NY (what is this?)  (verify)

Eletriptan (trade name Relpax, used in the form of eletriptan hydrobromide) is a second generation triptan drug intended for treatment of migraine headaches. It is used as an abortive medication, blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by Pfizer Inc. It is sold in the US and Canada under the brand name Relpax, and in several other countries under the brand name Relert.

Approval and availability

Eletriptan was approved by the U.S. Food and Drug Administration (FDA) on December 26, 2002, for the acute treatment of migraine with or without aura in adults. It is available only by prescription in the United States and Canada. It is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. It is available in 20 mg, 40 mg and 80 mg strengths.

Eletriptan is covered by U.S. Patent no. 5545644 and U.S. Patent no. 6110940; the FDA lists the patents as scheduled for expiration on December 26, 2016, and August 29, 2017, respectively.

Mechanism of action

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 a serotonin receptor agonist, specifically an agonist of certain 5-HT₁ family receptors. Eletriptan binds with high affinity to the 5-HT_{[1B, 1D, 1F]} receptors. It has a modest affinity to the 5-HT_{[1A, 1E, 2B, 7]} receptors, and little to no affinity at the 5-HT_{[2A, 2C, 3, 4, 5A, 6]} receptors.

Eletriptan has no significant affinity or pharmacological activity at adrenergic α₁, α₂, or β; dopaminergic D₁ or D₂; muscarinic; or opioid receptors. Eletriptan could be efficiently co-administrated 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.

Side effects

Common side effects include hypertension, tachycardia, headache, dizzyness, and symptoms similar to angina pectoris. Severe allergic reactions are rare.

Contraindications

Eletriptan is contraindicated in patients with various diseases of the heart and circulatory system, such as angina pectoris, severe hypertension, and heart failure, as well as in patients that have had a stroke or heart attack. This is due to the unusual side effect of coronary vasoconstriction due to serotonin 5HT_1B antagonism, which can precipitate a heart attack in those already at risk. It is also contraindicated in severe renal or hepatic impairment due to its extensive liver metabolism through CYP3A4.

Interactions

Strong inhibitors of the liver enzyme CYP3A4, such as erythromycin and ketoconazole, significantly increase blood plasma concentration and of eletriptan and should be separated by at least 72 hours. Ergot alkaloids, such as dihydroergotamine, add to the drug's hypertensive effect and should be separated by at least 24 hours.

Additional chemical names

• Merck Index: 3-[[(2R)-1-Methyl-2-pyrrolidinyl]methyl]-5-[2-(phenylsulfonyl)ethyl]-1H-indole
• 5-[2-(benzenesulfonyl)ethyl]-3-(1-methylpyrrolidin-2(R)-ylmethyl)-1H-indole
• (R)-5-[2-(phenylsulfonyl)ethyl]-3-[(1-methyl-2-pyrrolidinyl)methyl]-1H-indole

External links

• FDA label (December 2002)
• Physicians' Desk Reference entry for Relpax
• Medline Plus Drug Information for Eletriptan
• Pfizer Relpax site