Sumatriptan

Sumatriptan

Systematic (IUPAC) name
1-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]- N-methyl-methanesulfonamide
Clinical data
Trade names	Imitrex
AHFS/Drugs.com	monograph
Licence data	US FDA:link
Pregnancy cat.	C
Legal status	?
Routes	tablet, subcutaneous injection, nasal spray
Pharmacokinetic data
Bioavailability	15% (oral)/ 96% (s.c)
Protein binding	14%-21%
Metabolism	MAO
Half-life	2.5 hours
Excretion	60% urine; 40% feces
Identifiers
CAS number	103628-46-2 Y
ATC code	N02CC01
PubChem	CID 5358
IUPHAR ligand	54
DrugBank	DB00669
ChemSpider	5165 Y
UNII	8R78F6L9VO Y
KEGG	D00451 Y
ChEBI	CHEBI:10650 Y
ChEMBL	CHEMBL128 Y
Chemical data
Formula	C14H21N3O2S
Mol. mass	295.402 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C14H21N3O2S/c1-15-20(18,19)10-11-4-5-14-13(8-11)12(9-16-14)6-7-17(2)3/h4-5,8-9,15-16H,6-7,10H2,1-3H3 Y Key:KQKPFRSPSRPDEB-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Sumatriptan is a triptan sulfa drug containing a sulfonamide group. It is used for the treatment of migraine headaches. Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan, Imitrex, Imigran, Imigran recovery.

Approval and availability

Sumatriptan was the first clinically available triptan (in 1991). In the United States and most developed countries, it is available only by medical prescription. However, it can be bought over the counter in the UK in 50mg dosage if already prescribed for the patient. Several dosage forms for sumatriptan have been approved, including tablets, solution for injection, and nasal inhalers.

On April 15, 2008, the US FDA approved a combination of sumatriptan and naproxen, an NSAID. This combination has shown a benefit over either medicine used separately.

In July 2009, the US FDA approved a single-use jet injector formulation of sumatriptan. The device delivers a subcutaneous injection of 6 mg sumatriptan. A similar application has been filed in Europe.

Phase III studies with a iontophoretic transdermal patch (Zelrix) started in July 2008. This patch uses low voltage controlled by a pre-programmed microchip to deliver a single dose of sumatriptan through the skin within 30 minutes.

Mode of action

Sumatriptan is structurally similar to serotonin (5HT), and is a 5-HT (types 5-HT_1D and 5-HT_1B) agonist. The specific receptor subtypes it activates are present on the cranial arteries and veins. Acting as an agonist at these receptors, Sumatriptan reduces the vascular inflammation associated with migraine.

The specific receptor subtype it activates is present in the cranial and basilar arteries. Activation of these receptors causes vasoconstriction of those dilated arteries. Sumatriptan is also shown to decrease the activity of the trigeminal nerve, which, it is presumed, accounts for sumatriptan's efficacy in treating cluster headaches. The injectable form of the drug has been shown to abort a cluster headache within fifteen minutes in 96% of cases.

Pharmacokinetics

Sumatriptan is administered in several forms; tablets, subcutaneous injection, and nasal spray. Oral administration (as succinate) suffers from poor bioavailability, partly due to presystemic metabolism—some of it gets broken down in the stomach and bloodstream before it reaches the target arteries. A new rapid-release tablet formulation has the same bioavailability, but the maximum concentration is achieved on average 10–15 minutes earlier. When injected, sumatriptan is faster-acting (usually within 10 minutes), but the effect lasts for a shorter time. Sumatriptan is metabolised primarily by monoamine oxidase A into an indole acetic acid analogue, part of which is further conjugated with glucuronic acid. These metabolites are excreted in the urine and bile. Only about 3% of the active drug may be recovered unchanged.

There is no simple, direct relationship between sumatriptan concentration (pharmacokinetics) per se in the blood and its anti-migraine effect (pharmacodynamics). This paradox has, to some extent, been resolved by comparing the rates of absorption of the various sumatriptan formulations, rather than the absolute amounts of drug that they deliver.

Side-effects

Large doses of sumatriptan (200 mg/day) can cause sulfhemoglobinemia, a rare condition in which the blood changes from red to greenish-black, due to the integration of sulfur into the hemoglobin molecule. If sumatriptan is discontinued, the condition reverses within a few weeks.

Serious cardiac events, including some that have been fatal, have occurred following the use of Imitrex Injection or Tablets. Events reported have included coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation.^{[citation needed]}

The most common side-effects reported by at least 2% of patients in controlled trials of Imitrex (25, 50, and 100 mg tablets) for migraine are atypical sensations (paresthesias and warm/cold sensations) reported by 4% in the placebo group and 5-6% in the Imitrex groups, pain and other pressure sensations (including chest pain) reported by 4% in the placebo group and 6-8% in the Imitrex groups, neurological events (vertigo) reported by less than 1% in the placebo group and less than 1% to 2% in the Imitrex groups. Malaise/fatigue occurred in less than 1% of the placebo group and 2-3% of the Imitrex groups.

Generics

Sumatriptan vials 100 5509

On November 6, 2008, Par Pharmaceutical announced that it would begin shipping generic versions of Imitrex Injection (sumatriptan succinate injection) 4 mg and 6 mg starter kits and 4 mg and 6 mg pre-filled syringe cartridges to the trade immediately. In addition, Par anticipates launching the 6 mg vials early in 2009.

Mylan Laboratories Inc. has received FDA approval for its generic version of Imitrex tablets in 25-, 50-, and 100-milligram doses. The drug will soon be available, or is already available, in European markets, since Glaxo's patent protections have expired in those jurisdictions. However, sales of the generic drug are still restricted in the U.S., since Glaxo won an extension on their patent until 2009. A generic version of the drug in tablet form became available December 2008 in the United States and is distributed by Ranbaxy.

See also Sumavel DosePro (above).

Chemistry

U.S. Patent 4,785,016