Sumatriptan succinate Chemical Properties

Melting point:

165-166°C

storage temp. 

-20°C

solubility 

H2O: >20mg/mL

form 

solid

color 

white to off-white

Merck 

14,8997

BCS Class

3

InChIKey

PORMUFZNYQJOEI-UHFFFAOYSA-N

CAS DataBase Reference

103628-48-4(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38-41

Safety Statements 

26-36-39

RIDADR 

3077

WGK Germany 

3

RTECS 

EJ9940000

HS Code 

29350090

Sumatriptan succinate Usage And Synthesis

Description

Sumatriptan succinate is a synthetic drug belonging to a class of medications known as 5-hydroxytryptamine agonists (also called "triptans"), which is commonly used to treat cluster and migraine headaches with or without aura (warning signs occurring prior to the onset of a migraine). It is effective to relieve or eliminate the intensity of migraine and cluster headaches and accompanying symptoms including sensitivity to light or sound, nausea, and vomiting. However, it cannot help prevent future migraines/headaches or decrease the frequency of getting migraine and it is not recommended for other types of headache or for headache prevention.
It is believed that the pain of migraine headaches is induced by dilated blood vessels inside the head. Sumatriptan succinate relieves migraine headaches by affecting the serotonin in the brain, which results in constriction of blood vessels. Subcutaneous injection of this drug is more effective than other formulations.

References

https://en.wikipedia.org/wiki/Sumatriptan
http://www.medicinenet.com/sumatriptan_succinate-injection/article.htm
http://bodyandhealth.canada.com/drug/getdrug/teva-sumatriptan-df
http://www.webmd.com/drugs/2/drug-7741/sumatriptan-oral/details

Description

Sumatriptan succinate is a highly selective 5HT₁-like receptor agonist introduced as a new treatment for migraine. It is indicated for the acute relief of migraine and cluster headache. Oral administration is reported to be free of substantial side effects. The compound appears to be a significant advance over the use of ergotamine and other agents in the treatment of migraine.

Chemical Properties

White Crystalline Powder

Originator

Glaxo (United Kingdom)

Uses

A serotonin 5HT1-receptor agonist

Uses

H1-antihistamine

Uses

A selective 5-HT1 receptor agonist

Uses

Sumatriptan (succinate) is a serotonin 5-hydroxytryptamine 1 (5-HT1) receptor agonist with selective affinity for 5-HT1B and 5-HT1D receptors with IC50 values of 9.3 and 7.3 nM, respectively. It also has affinity for the 5-HT1F receptor (IC50 = 17.8 nM). Sumatriptan (succinate) has been shown to induce vasoconstriction of human middle meningeal arteries (EC50 = 89.9 nM) and reduce vascular inflammation associated with migraines.

Uses

Sumatriptan Succinate is a selective 5-HT1B/1D-receptor agonist with anticonvulsant properties (1,2). Sumatriptan Succinate is used for migraine relief (2).

Definition

ChEBI: A succinate salt obtained by reaction of sumatriptan with one equivalent of succinic acid. Selective agonist for a vascular 5-HT1 receptor subtype (probably a member of the 5-HT1D family). Used for the acute treatm nt of migraine with or without aura in adults.

Manufacturing Process

A solution of (phenylthio)acetaldehyde (6.05 g) in absolute ethanol (180 ml) was added over 10 min to a solution of 4-hydrazino-Nmethylbenzenemethanesulphonamide hydrochloride (10 g) in water (180 ml) with cooling. After addition of the aldehyde was complete, the mixture was stirred at 5°C for a period of 14 h. The precipitated solid was filtered off, washed with water (200 ml), hexane (200 ml) and dried in vacuo to give the N-methyl-4-[2-[2-(phenylthio)ethylidene]hydrazino]benzenemethanesulphonamide (10.95 g), melting point 110°-112°C.
A solution of the N-methyl-4-[2-[2- (phenylthio)ethylidene]hydrazino]benzenemethane-sulphonamide in absolute ethanol (300 ml) was saturated with hydrogen chloride gas (ca. 30 min) whilst being cooled in an ice-water bath, allowed to stir at room temperature for 3 h and filtered. The filtrate was concentrated in vacuo and chromatographed to afford a foam, which solidified on trituration with ether to an amorphous powder (2.17 g). A sample was recrystallized from hexane-dichloromethane to give the N-methyl-3-(phenylthio)-1H-indole-5-methanesulphonamide, melting point 133°-134°C.
To a solution of N-methyl-3-(phenylthio)-1H-indole-5-methanesulphonamide (460 mg) in absolute ethanol (50 ml) was added Raney nickel [4.6 g, 50% slurry in water, washed to neutrality with deionized water (60 ml)] and the reaction mixture refluxed for 16 h under an atmosphere of nitrogen. On cooling to room temperature, the supernatant was removed and the Raney nickel extracted with ethanol (2x50 ml, which was brought to a gentle reflux for 15 min under an atmosphere of nitrogen). The combined extracts were filtered through a sand-celite pad and concentrated in vacuo. Chromatography of the residue, afforded an oil (87 mg) which crystallized from ether-hexane to give the N-methyl-1H-indole-5-methanesulphonamide (90 mg), melting point 127°-129°C.
To N,N-diethyl chloroacetamide (800 mg) at 0°C was added phosphorous oxychloride (250 μl) over a period of 30 sec. After the addition was complete, the mixture was allowed to stir at 0°C for 15 min and then at room temperature for 20 min. The N-methyl-1H-indole-5-methanesulphonamide (300 mg) was added at 0°C and the mixture warmed to 65°C, whereupon it dissolved. The mixture was stirred for 2 h at this temperature then poured onto ice (ca. 5 g) and chloroform (5 ml) and stirred vigorously for 1 h. A solid was filtered off, washed with water (50 ml), and hexane (100 ml) and dried in vacuo to give the 3-(chloroacetyl)-N-methyl-1H-indole-5- methanesulphonamide (192 mg).
A solution of the 3-(chloroacetyl)-N-methyl-1H-indole-5- methanesulphonamide (160 mg) in ethanolic dimethylamine (30 ml, 33% w/v solution in ethanol) was heated to reflux for 2 h. On cooling to room temperature the solvent was removed in vacuo and the residue was chromatographed to afford the 3-[(dimethylamino)acetyl]-N-methyl-1Hindole- 5-methanesulphonamide, melting point 230°C, dec.
To a suspension of the 3-[(dimethylamino)acetyl]-N-methyl-1H-indole-5- methanesulphonamide (46.5 mg) in 1-propanol (5 ml) was added sodium borohydride (62 mg). The reaction mixture was brought to reflux for a period of 3 h, then an additional quantity of borohydride (60 mg) was added. After refluxing for a further 1 h, the mixture was allowed to cool to room temperature and quenched with 2 N HCl (10 ml). The aqueous solution was washed with ethyl acetate (5 ml) then neutralized (NaHCO3 solution) and extracted with ethyl acetate (3 x 15 ml). The combined extracts were concentrated in vacuo and the residue chromatographed to give the 3-[2- (dimethylamino)ethyl]-N-methyl 1H-indole-5-methanesulphonamide as a gum (2 mg) which was shown by TLC.
Succinic acid in hot methanol was added to a hot solution of the the 3-[2- (dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide in absolute ethanol and the mixture was heated to reflux with stirring to give a solution. The solution was allowed to cool with stirring to room temperature, and the resultant suspension was farther cooled in an ice-bath for 2 h. The solid was filtered off, washed with ethanol, and dried in vacuo to give the 3- [2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide, salt with succinic acid (1:1).

brand name

Imitrex (GlaxoSmithKline);Imigran.

Therapeutic Function

Serotoninergic

World Health Organization (WHO)

Suprofen, a nonsteroidal anti-inflammatory agent, was introduced in 1983 for use as an analgesic for the symptomatic relief of mild to moderate pain and for primary dysmenorrhoea. By 1986 it had become evident that its use was occasionally associated with flank pain sometimes accompanied by evidence of decreased renal function. The Arthritis Advisory Committee of the United States Food and Drug Administration met in December 1986 to review the situation and decided against withdrawing suprofen from the market. However, in May 1987 the Committee for Proprietary Medicinal Products of the European Community recommended that all marketing authorizations should be suspended. The manufacturer subsequently decided to suspend sale worldwide on the grounds that sales had diminished to the point where the product was no longer economically viable.

Biological Activity

Selective 5-HT 1 receptor agonist (K i values are 17, 27 and 100 nM at 5-HT 1D , 5-HT 1B and 5-HT 1A receptors respectively). Antimigraine agent.

Biochem/physiol Actions

Sumatriptan succinate is a 5-HT1 serotonin receptor agonist.

storage

+4°C

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