3661. Ergotamine

Nomenclature

CAS number: 113-15-5
(5′α)-12′-Hydroxy-2′-methyl-(phenylmethyl)ergotaman-3′,6′,18-trione.
C33H35N5O5; mol wt 581.66.
C 68.14%, H 6.07%, N 12.04%, O 13.75%.

Description and references

Vasoconstrictor found in ergot of Central Europe. Extraction procedure: Stoll, Helv. Chim. Acta 28, 1283 (1945). Pharmacology: E. Rothlin, Schweiz. Med. Wochenschr. 76, 1254 (1946). Structure: Stoll et al., ibid. 34, 1544 (1951). Total synthesis: Hofmann et al., Experientia 17, 206 (1961). Stereochemistry: Hofmann et al., ibid. 46, 2306 (1963). Comprehensive description: B. Kreilgard, Anal. Profiles Drug Subs. 6, 113-159 (1977). LC determn in tablets: U. R. Cieri, J. Assoc. Off. Anal. Chem. 70, 538 (1987); GC/MS determn in plasma: N. Feng et al., J. Chromatogr. 575, 289 (1992). Bioavailablity and efficacy in migraine: V. Ala-Hurula, Headache 22, 167 (1982). Review of clinical pharmacokinetics and treatment of headache: V. L. Perrin, Clin. Pharmacokinet. 10, 334-352 (1985). Review of teratogenic risk: G. V. Raymond, Teratology 51, 344-347 (1995).

Chemical structure

Properties

Elongated prisms from benzene. Very hygroscopic. Darkens and dec on exposure to air, heat and light. Dec 212-214°. [α]D20 -160° (chloroform). Sol in about 70 parts methanol, 150 parts acetone, 300 parts alcohol; freely sol in chloroform, pyridine, glacial acetic acid; moderately sol in ethyl acetate; slightly in benzene. Almost insol in water, petr ether. LD50 in mice, rats, rabbits (mg/kg): 62, 80, 3 i.v.; in cats: 11 s.c. (Rothlin).

Derivative

Hydrochloride.
C33H35N5O5.HCl; mol wt 618.12.
C 64.12%, H 5.87%, N 11.33%, O 12.94%, Cl 5.74%.

Properties

Rectangular plates from 90% alc, mp 212° (dec). Sol in water-alcohol mixtures; sparingly in water or alcohol.

Derivative

Tartrate.

Nomenclature

CAS number: 379-79-3
Ergomar (Lotus); Ergostat (Warner-Lambert); Gynergen (Novartis); Lingraine (Sanofi-Synthelabo).
(C33H35N5O5)2.C4H6O6; mol wt 1313.41.
C 64.01%, H 5.83%, N 10.66%, O 19.49%.

Properties

Solvated crystals, e.g. the dimethanolate, heavy rhombic plates from methanol, mp 203° (dec). [α]D25 -125 to -155° (c = 0.4 in chloroform). One gram dissolves in 500 ml water or 500 ml alc. Protect from heat and light.

Therapeutic Category

Antimigraine.

Therapeutic Category (Veterinary)

Tartrate has been used as an oxytocic.

Keywords

Antimigraine; Serotonin Receptor Agonist