Ergotamine

Molecular formula C33 H35 N5O5 Molecular weight 581.66 CAS Registry No 113-15-5 Merck Index 13,3696 

Guard column 40 mm long 4 (Xm Purospher RP-18 LiChro Cart 4-4 

Mobile phase Gradient. MeCN buffer from 20 80 to 100 0 over 10 min, maintain at 0 100 for 3 min, re-equUibrate at initial conditions for 5 min. (The buffer was 10 mM ammonium acetate containing 0.1% formic acid (pH 3.2).) 

Detector MS, PE Sciex API 365 triple-stage quadrupole LC-MS-MS, PE Sciex Turbolon-Spray interface, positive ion mode, needle voltage 5.2 kV, nebulizer gas air at 60 psi, curtain gas nitrogen at 40 psi, coUision cell gas nitrogen at 40 psi, turbo ionspray heater 375°, heater gas flow 7 L/min 

Gergov, M. Ojanpera, I. Vuori, E. Simultaneous screening for 238 drugs in blood by liquid chromato-graphy-ionspray tandem mass spectrometry with multiple-reaction monitoring, J.Chromatogr.B, 2003, 795, 41-53. 

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Acyl azides may loose N2 on heating and rearrange to isocyanates (Curtius rearrangement), which may be solvolyzed. Some of the possibilities of classical carboxyl conversions are exemplified in the schemes below, which are taken from a triquinacene synthesis (R. Russo, 1971 C. Merder, 1973) and the ergotamine synthesis of A. Hofmann (1963). 

There are currently two medicinally valuable alkaloids of commercial import obtained from ergot. Commercial production involves generation parasiticaHy on rye in the field or production in culture because a commercially useful synthesis is unavailable. The common technique today (65) is to grow the fungus in submerged culture. Clavicepspaspali (Stevens and Hall) is said to be more productive than C. purpurea (Fries). In this way, ergotamine (100,... 

R =101) and ergonovine (100, R = NHCH(CH3)CH20H) are produced. Ergotamine is obtained from cmde extract by formation of an aluminum complex which can then be defatted. 

The lungs large, permeable surface makes systemic deUvery possible. For example, an inhaler deUvers 360 )Tg per dose of aerosolized ergotamine tartrate [379-79-3] for migraine (54), and inhalant systems deUver anesthetic gases. Research is under way on the systemic deUvery of proteins and peptides through the lungs (57,58). 

Pellotine is a convulsant in the frog and cat. Clerc, Janot and Paris, state that the intravenous lethal dose in dogs is 10 mgm./kilo. In chloralosed dogs 5 mgm./kilo slowed the heart and caused a fall in blood pressure the effects lasted for a few minutes and resembled those due to acetylcholine they were inhibited by atropine and increased by yohimbine and ergotamine. A few injections of this dose at short intervals produced convulsions and this effect was inhibited by phenobarbitone. 

Ergotamine crystallises from a variety of solvents but always with the solvent, e.g., from aqueous acetone, which is recommended as a medium, it separates in rectangular plates, B. 2H2O. 2C3HgO, decomposes at 180° and has, for solvent free base, [a] ° — 160° and — 192° (c = 1 CHCl3)or 12-7°and [a] 4g°—8-6°(c= 1 pyridine). Kdder ... 

Ergotamine, like ergotoxine, is unstable, especially in aqueous solutions of its salts exposed to light the rate of deterioration for both alkaloids has been measured by Wokes and Elphick. ... 

Ergotamine —ergotaminine. Pyruvic acid, d-proline, Z-phenylalanme. > Ergosine—ergosinine. Pyruvic acid, d-proline, Z-leucine. ... 

Useful general articles on the pharmacology of the ergot alkaloids have been published by Nelson and Calvery, Wliite, " and Barger, and monographs on ergotamine and the alkaloids of ergot by StoU (1945). ... 

Bellacane Elixir—atropine, scopolamine HBr, hyoseyamine HBr or sulfate, phenobarbital, alcohol, tartrazine Bellacane SR Tablets—1-alkaloids of belladonna, phenobarbital, ergotamine tartrate Bellergal-S Tablets—1-alkaloids of belladonna, phenobarbital, ergotamine tartrate Butibel Elixir—belladonna extract, butabarbital sodium, alcohol, sucrose, saccharin Butibel Tablets—belladonna extract, butabarbitol Chardonna-2 Tablets—belladonna extract, phenobarbital Donnatal Elixir—atropine, scopolamine HBr, hyoseyamine HBr or sulfate, phenobarbital, alcohol, sucrose, saccharin... 

A series of corresponding ergoline and ergolene derivatives was synthesized. The ergotamine derivative showed an interesting antihypertensive activity. Unfortunately, the substance has very poor solubility and stability and therefore the further pharmacological evaluation was stopped (ref. 25). 

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