Sumatriptan

Structural formula
General
Non-proprietary name	Sumatriptan
other names	1- [3- (2-dimethylaminoethyl) -1 H -indol-5-yl] - N -methyl-methanesulphonamide; 3- [2- (dimethylamino) ethyl] - N -methyl-5-indole methanesulfonamide;
Molecular formula	C 14 H 21 N 3 O 2 S
External identifiers / databases
EC number	600-462-9
ECHA InfoCard	100.130.518
PubChem	5358
DrugBank	DB00669
Wikidata	Q416978
Drug information
ATC code	N02 CC01
Drug class	Triptans
Mechanism of action	selective serotonin agonist
properties
Molar mass	295.40 g · mol -1
Physical state	firmly
Melting point	169-171 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 361-412
	P: ?
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Sumatriptan is a drug from the triptan group and is used for the acute therapy of migraines and cluster headaches .

Clinical information

Application areas (indications)

Sumatriptan- containing medicines are approved for the acute treatment of migraines with or without aura . The injection dosage form is also approved for the treatment of cluster headaches.

Contraindications (contraindications)

Sumatriptan must not be used in patients with a heart attack , suspected ischemic heart disease, coronary vasospasm ( Prinzmetal's angina ), peripheral blood vessel disorders , moderate to severe or uncontrolled high blood pressure . Sumatriptan should also not be used in the case of known severe liver dysfunction and a history of transient ischemic attacks.

Sumatriptan must not be used at the same time as ergot alkaloids and their derivatives (e.g. ergotamine , dihydroergotamine ), as there is an increased risk of vasospasm. Sumatriptan should also be used no earlier than two weeks after the end of treatment with monoamine oxidase inhibitors , as these inhibit the breakdown of sumatriptan.

Sumatriptan must not be used in the case of known hypersensitivity to the active substance. Particular caution is also required in the case of a known allergy to sulfonamides .

Use during pregnancy and breastfeeding

There is currently insufficient experience with its use in pregnancy . Previous experience does not indicate an increased risk of malformations during pregnancy. However, animal studies in rabbits have shown an embryotoxic effect of sumatriptan.

Sumatriptan is excreted in breast milk . Any potential risk to the child can be avoided by expressing and discarding breast milk up to 12 hours after taking sumatriptan.

Side effects

One of the most frequently discussed, albeit rare, side effects of the use of sumatriptan is angina pectoris- like pressure and tightness in the chest, which are attributed to a constriction of the coronary arteries . In animal experiments, however, it was only possible to produce a narrowing of the coronary arteries with much higher concentrations of the substance in the blood . An increase in blood pressure can also be observed in some patients.

Taken in high doses, the color of the blood can change green-black. This is called sulfhemoglobinemia and is caused by the fact that the sulfur contained in the substance in the form of a sulfonamide group is incorporated into hemoglobin. In an average-sized adult male, 200 mg a day can cause this color change.

Interactions

Although the data are limited, there is a risk of aggravating the side effects of ergot alkaloids when used concomitantly with sumatriptan. Sumatriptan should therefore not be used in combination with ergotamine (see contraindications). After using ergotamine, a safety interval of at least 24 hours before sumatriptan therapy should be observed; in the opposite case, the minimum interval should be 6 hours.

MAOIs can increase the effects and side effects of these substances by inhibiting the breakdown of sumatriptan and the body's own serotonin. Therefore, the simultaneous use of sumatriptan and MAOIs is contraindicated.

In rare cases, when a triptan and an antidepressant from the group of SSRIs (selective serotonin reuptake inhibitors) or SNRI (selective serotonin and noradrenaline reuptake inhibitors) are taken at the same time, potentially life-threatening interactions of the serotonin syndrome occur. Too much serotonin accumulates in the nervous system and its effect is intensified by sumatriptan. Symptoms of serotonin syndrome can include restlessness, hallucinations, loss of coordination, rapid heartbeat, fluctuations in blood pressure, increased body temperature, increased reflexes, nausea, vomiting, diarrhea, and death.

pharmacology

Mechanism of action

Sumatriptan is a selective agonist at the serotonin receptors 5-HT _1B , 5-HT _1D and 5-HT _1F , which occur on cerebral blood vessels and presynaptically on neurons . Activation of these receptors by sumatriptan leads to a narrowing of the enlarged (dilated) cerebral blood vessels during a migraine attack. On the other hand, sumatriptan leads to a reduction in the release of inflammatory mediators such as serotonin, calcitonin gene-related peptides (CGRP) and substance P, which dilate blood vessels and cause pain .

Since sumatriptan has poor oral bioavailability and can only insufficiently cross the blood-brain barrier , numerous so-called "2nd generation triptans" with improved pharmacokinetic properties have been developed.

Pharmaceutical information

Sumatriptan was the first triptan to be approved for medicinal purposes and came onto the market in 1991 under the brand name Imitrex (USA) and a little later as Imigran (D, CH, A). Since the drug's patent protection expired in May 2006, numerous generics are now available. Various forms of application are available for sumatriptan . In addition to oral dosage forms (tablets with 50 or 100 mg), non-oral sumatriptan preparations such as suppositories, nasal sprays, pre-filled syringes or pens for subcutaneous administration are also approved. Non-oral dosage forms can be advantageous, particularly in the case of pronounced migraine nausea with vomiting. Nasal and subcutaneous dosage forms should enable a faster onset of action. The low oral bioavailability can be circumvented by subcutaneous administration of the active ingredient.

A firm combination of sumatriptan with naproxen has been on the market in the United States since 2008. In January 2013, sumatriptan was iontophoresis - paving in the United States admitted .

literature

A. Schuurmans, C. van Weel: Pharmacologic treatment of migraine. Comparison of guidelines. In: Can Fam Physician. 51, June 2005, pp. 838-843. PMID 15986940