B. Ergotamine
Biological Source It is obtained from the seeds of Claviceps purpurea (Fr.) Tul. (Hypocreales) (Ergot).
Chemical Structure The chemical structure of ergotamine has been given in Section 7.2.8.6.
Isolation The method of Stoll* may be adopted as stated below:
1. The powdered dried ergot is first defatted with n-bexane or petroleum ether (40-60°)
2. The marc consisting of the defatted powdered ergot is thoroughly mixed with aluminium sulphate and water so as to fix the alkaloids by converting them into the double salts.
3. The resulting alkaloidal double salts are subjected to continuous extraction with hot benzene that removes the alkaloid exclusively on one hand; and the unwanted substances e.g., ergot oil, soluble acid, neutral substances like-phytosterol, colouring matter and organic acids on the other.
4. The benzene is removed under vacuo and the residue thus obtained is stirred for several hours with a large volume of benzene and subsequently made alkaline by passing NH3 gas.
5. The resulting solution is filtered and the benzene extract is concentrated under vacuo to approximately 1/50th of the original volume, whereupon ergotamine crystallizes out.
6. An additional quantity of ergotamine may also be crystallized from the mother liquour by treatment with petroleum ether.
7. Ergotamine may be further purified by crystallization from aqueous acetone.
Characteristic Features
1. It is obtained as elongated prisms from benzene that get decomposed at 212-214°C.
2. It usually becomes totally solvent-free only after prolonged heating in a high vacuum.
3. It is found to be highly hygroscopic in nature; and darkens and decomposes on exposure to air, heat and light.
4. It has specific optical rotation [α]20D - 160° (chloroform).
5. It is soluble in 70 parts methanol, 150 parts acetone, 300 parts ethanol; freely soluble in chloroform, pyridine, glacial acetic acid; moderately soluble in ethyl acetate; slightly soluble in benzene; and practically insoluble in petroleum ether and water.
Identification Tests The precipitation reactions and the colour tests are the same as described under ergonovine. However, the specific derivatives of ergotamine are as stated below:
1. Ergotamine Tartrate [(C33H35N5O5)2.C4H6O6] (Ergomar; Ergate; Ergotartrat; Ergostat; Exmigra; Fermergin; Lingraine; Gynergen; Lingran): It is normally obtained as solvated crystals e.g., the dimethanolate; also occurs as heavy rhombic plates from methanol having mp 203°C (decomposes). It has specific optical rotation [α]25D – 125° to – 155° (C = 0.4 in chloroform). One gram dissolves in either 500 ml of ethanol or water.
2. Ergotamine Hydrochloride [C33H35N5O5.HCl]: It is obtained as rectangular plates from 90% (v/v) ethanol which get decomposed at 212°C. It is found to be soluble in water-ethanol mixtures; and sparingly in water or ethanol alone.
3. Dihydroergotamine Mesylate (C33H37N5O5.CH3SO3H) (Agit;1 Dihydro-ergotamine methane sulphonate; Angionorm; DET MS; Dergotamine; D.H.E. 45; Diergo; Dihydergot; Dirgotarl; Endophleban; Ergomimet; Ikaran; Migranal; Morena; Ergont; Ergotonin; Orstanorm; Tonopres; Verladyn; Seglor): It is obtained as large prisms from 95% (v/v) ethanol having mp 230-235°C; and moderately soluble in water.
Note: (a) It is the salt of a semisynthetic alkaloid prepared from ergotamine by hydrogenation of the ∆9 double bond in the lysergic acid nucleus.
(b) It is mostly used in the treatment of migraine because it is found to be better in efficacy and more tolerated than the parent alkaloid.
Uses
1. It is employed as a potent antimigraine drug.
2. Ergotamine possesses oxytocic properties, but it is not employed for that effect.
3. Ergotamine tartrate is used invariably to prevent or abort vascular headaches, including migraine and cluster headaches. The mechanism of action is perhaps due to direct vasoconstriction of the dilated carotid artery bed with concomitant lowering in the amplitude of pulsations.
4. Ergotamine tartrate is also an antagonist of the serotonin activity.
5. Ergotamine tartrate is frequently used along with caffeine for the management and control of migraine headache. Both serve as cerebral vasoconstrictors; while the latter is considered to increase the action of the former.
6. Methylergonovine maleate is an oxytocic reported to be longer acting and more active than ergonovine.
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* Stoll, Helv. Chim. Acta 28, 1283, (1945)
