methysergide Property

Melting point:

194-196°

alpha 

D20 -45° (c = 0.5 in pyridine)

Boiling point:

486.87°C (rough estimate)

Density 

1.1377 (rough estimate)

refractive index 

1.6300 (estimate)

storage temp. 

Amber Vial, -20°C Freezer, Under inert atmosphere

solubility 

Chloroform (Slightly), Methanol (Slightly), Pyridine (Slightly)

form 

Solid

pka

pKa 6.62± 0.02(H2O,t =24,I<0.01)(Approximate)

color 

Off-White

Stability:

Light Sensitive

Safety

Hazardous Substances Data

361-37-5(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

methysergide Chemical Properties,Usage,Production

Originator

Sansert,Sandoz,US,1962

Uses

Methysergide (Methylergonovine EP Impurity G) is a serotonergic receptor antagonist.

Uses

Vasoconstrictor (specific in migraine).

Definition

ChEBI: (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide is an ergoline alkaloid.

Manufacturing Process

As described in US Patent 3,218,324, 0.9 part of potassium are dissolved in 500 parts by volume of liquid ammonia, then oxidized with ferric nitrate to potassium amide, after which 4.85 parts of lysergic acid-1'-hydroxybutylamide-2' are dissolved in the obtained mixture. After 15 minutes there are added to the obtained yellow solution 4.1 parts of methyl iodide in 5 parts by volume of ether, the mixture being allowed to stand for 30 more minutes at -60°C. The liquid ammonia is thereupon evaporated and the dry residue is shaken out between water and chloroform. The mixture of bases which remains after the evaporation of the chloroform is chromatographed on a column of 250 parts of aluminum oxide, the desired 1-methyl-lysergic acid-1'- hydroxy-butylamide-2' being washed into the filtrate with chloroform and chloroform-0.2% ethanol. The 1-methyl-lysergic acid-1'hydroxy-butylamide-2' crystallizes from chloroform in the form of plates which melt at 194° to 196°C. Reaction with maleic acid gives the dimaleate, melting at 187° to 188°C.

Therapeutic Function

Migraine therapy

Clinical Use

Methysergide (Sansert), which is structurally identical to methylergonovine except for the addition of a methyl group to the indole nitrogen, has far less of the uterine stimulatory properties of the other agents and, instead, is used exclusively for treatment of migraine headache as a serotonin antagonist at 5-HT1/5-HT2 receptors.Methysergide is a potent peripheral inhibitor of 5-HT receptors in the blood vessel, which inhibits vessel-wall permeability. Methysergide also inhibits the release of histamine from mast cells and stabilizes platelets against the release of 5-HT, which may be responsible for the onset of the migraine attack. In contrast to its peripheral effects, methysergide appears to be a central 5-HT1 agonist, resulting in alleviation of the central hyperalgesia effect that occurs in patients with migraine.