Ergotamine preparation

H. Bethke, B. Delz, and K. Stich, Determination of the content and purity of ergotamine preparations by means of HPLC, J. Chromatogr., 123 193 (1976). 

Ergta.Ergtaine, aciErgta.aciErg-taine.Lysam.iso-Lysam,Lysac,iso-Lysac.lumiErgta Quality control ergotamine preparations (Table 9.2)... 

Ergotamine preparations have lost some of their popularity due to the availability of stronger and more tolerable dopaminer-gics, and acetylcholinesterase inhibitors are regarded as being obsolete due to their negative effects on cognition. 

Ausband SC, Goodman PE An unusual case of clarithromycin associated ergotism. J Emerg Med 2001 21(4) 411-413. [PMID 11728770] (Lower-extremity vasospasm due to addition of clarithromycin in a patient with longstanding use of a caffeine-ergotamine preparation for migraine.)... 

The following countries have reported seizures of preparations containing ergometrine and ergotamine ... 

Contraindications Basilar or hemiplegic migraine, coronary artery disease, ischemic heart disease (including angina pectoris, history of Ml, silent ischemia, and Prinzmetal s angina), uncontrolled hypertension, use within 24 hours of ergotamine-contain-ing preparations or another serotonin receptor agonist, use within 14 days of MAOls... 

Fixed dose combinations of crude ergot preparations except those containing ergotamine, caffeine, analgesics, antihistamines for the treatment of migraine, headache. 

The total synthesis of ergotamine (34) opened new possibilities for the preparation of new stereoisomers. Theoretically, almost every isomer now became accessible. 

Protoplasts of C. purpurea have been prepared which are able to synthesize the peptidic ergot alkaloids ergotamine (69) and ergocryptine de novo.63 Various radioactive amino-acids were incorporated into the alkaloids, and D-lysergic acid (70) stimulated their utilization. It was the only precursor to stimulate the synthesis of alkaloids, and the proposal was made that the concentration of (70) in the cells is a rate-limiting factor in alkaloid synthesis. 

With the preparation of pure ergotamine, chemical research on ergot also entered a new phase so that, after many decades, it finally became possible to elucidate the structure of the ergot alkaloids and to achieve their total synthesis. This will be shown in the remainder of this chapter. 

Salts of ergotamine. Ergotaminetartrate (CssH OsNs. C4H6O6. 2CH3OH, from methanol thick rhombic slabs, mp 203°, is the salt of ergotamine most used in pharmaceutical preparations (e.g., Gynergen, Bellergal) and this salt is the one which has been adopted by the pharmacopeias. 

The literature on pharmacological and clinical investigations of the ergot alkaloids and their derivatives is very comprehensive. There have already been more than one-thousand reports on lysergic acid diethylamide (LSD 25) (66), which was prepared only 20 years ago the publications on the pharmacological and clinical effects of ergotamine (13, 14), which was isolated in 1918, are far greater in number. In this review it will therefore not be possible to go into details it will be based on a schematic representation provided by Cerletti (170) and further elaborated by Hofmann (171). 

ERGOTAMINE GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects, e.g. vasospasm, ergotism, peripheral vasoconstriction, gangrene Possibly t bioavailability by 1 presystemic metabolism. Constituents of grapefruit juice irreversibly inhibit intestinal cytochrome CYP3A4 Monitor for t side-effects and stop intake of grapefruit preparations if side-effects occur... 

Spontaneous intracerebral hemorrhage occurred in a 72-year-old woman who had been taking GB 50 mg three times daily for 6 months (54). Bilateral subdural hematomas were discovered in a 33-year-old woman who had been taking 60 mg of GB twice daily for 2 year, acetaminophen, and occasionally an ergotamine/caffeine preparation (55). Bleeding time was elevated, but had normalized when checked approx 1 month after discontinuation of the product. 

IV use ischemic heart disease silent ischemia, Prinzmetal s angina, uncontrolled hypertension, concurrent ergotamine-containing preparations, hemiplegic or basilar migraine Caution with liver and kidney problems... 

Fluorimetric ion-pair chromatography has been applied for ergotamine, ergotaminine and dihydroergotamine in connection with the analysis of pharmaceutical preparations containing tropane alkaloids 36,30,3 (Chapter 4). 

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