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Sumatriptan

Systematic (IUPAC) name
1-[3-(2-dimethylaminoethyl)-1H-indol-5-yl]- N-methyl-methanesulfonamide
Identifiers
CAS number	103628-46-2
ATC code	N02CC01
PubChem	CID 5358
IUPHAR ligand ID	54
DrugBank	APRD00379
ChemSpider	5165
Chemical data
Formula	C14H21N3O2S
Mol. mass	295.402 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	15% (oral)/ 96% (s.c)
Protein binding	14%-21%
Metabolism	MAO
Half-life	2.5 hours
Excretion	60% urine; 40% feces
Therapeutic considerations
Licence data	US FDA:link
Pregnancy cat.	C
Legal status
Routes	tablet, subcutaneous injection, nasal spray
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Sumatriptan (trade names Imitrex, Imigran, Imigran recovery) is a triptan drug including a sulfonamide group for the treatment of migraine headaches. Imitrex is marketed and manufactured by GlaxoSmithKline as well as various generic drug manufacturers.

[edit] Approval and availability

Sumatriptan was the first triptan available (in 1991), and, in the United States and most developed countries, is available only by medical prescription. Several dosage forms for sumatriptan have been approved, including tablets, solution for injection, and nasal inhalers.

In the United Kingdom, sumatriptan is available over the counter, under the name Imigran Recovery. It is sold in packs of two 50 mg tablets for approximately £7.99 (equivalent to about $12 US). In the U.S. the cost in 2009 is about $15. Larger pack sizes, a nasal spray preparation, and a liquid preparation for injection are also available by prescription. Patent Protection in the UK and Europe expired on 16 May 2006, under UK Patent GB2162522 (extended by supplementary protection certificate SPC/GB93/07). In the United States, Glaxo Smith Kline was able to extend their US patent considerably beyond this date through patent litigation. However, a generic injectable version of sumatriptan came to market in August 2008 (Dr Reddy's Labs Ltd).^{[citation needed]}

On April 15, 2008, the US FDA approved a combination of sumatriptan and naproxen, an NSAID, which is marketed in the USA under the trade name Treximet.^[1]. This combination has shown a benefit over either medicine used separately.^[2]

In July 2009, the United States FDA approved Sumavel DosePro(R) (Zogenix Inc., Emeryville and San Diego, California, USA). This is a unique pre-filled, single-use delivery system for 6 mg subcutaneous sumatriptan. It has no needle, and uses gas pressure as a power source. The drug is delivered in less than 100 msec. Sumavel DosePro is about the size of a white board marker or fat felt-tipped pen, and became available for prescription in the USA in early 2010; a corresponding product application has been filed in Europe.^[3]

Phase III studies with a iontophoretic transdermal patch (Zelrix) started in July 2008.^[4] This patch uses low voltage controlled by a pre-programmed microchip to deliver a single dose of sumatriptan through the skin within 30 minutes.^[5][6]

[edit] Mode of action

Sumatriptan is structurally similar to serotonin (5HT), and is a 5-HT (types 5-HT_1D and 5-HT_1B^[7]) 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.

[edit] 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.^[8][9]

[edit] 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.^[10] 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.

In the below table, "Common" is reported in at least 1/100 patients, "Less common" in 1/100 to 1/1000 patients and "Rare" in less than 1/1000 patients^[11]. It should be noted that some of the symptoms listed below are classic symptoms associated with migraine itself, such as photo/phonophobia, visual disturbances, and nausea.

[edit] Generics

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.^[12]

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).^[3]

[edit] Chemistry

U.S. Patent 4,785,016

[edit] References

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Sumatriptan".