Curare erythrina alkaloids

Alkaloids of Curare Curine, Tubocurarine, Protocuridine, Calabash-curare I, etc., including Erythrina alkaloids Alkaloids of Ipecacuanha. ... 

Erythrina alkaloids, possessing curare-like activity, are a large class of natural products found in Erythrina plants (Leguminosae). In a study towards construction of the erythrina skeleton, disfavored 5-endo-trig cyclizations were achieved by Ikeda et al. by BusSnH-mediated radical cyclization of an //-vinylic a-chloroacetamide to give five-membered lactams... 

Many Erythrina alkaloids possess curare-like action. Alkaloidal extracts from different parts of Erythrina species have been used in indigenous medicine, particularly in India (176). Many pharmacological effects, including astringent, sedative, hypotensive, neuromuscular blocking, CNS depressant, laxative, and diuretic properties, have been recorded for total alkaloid extracts, although not all these properties can be associated with the ery-thrinane structure alone (38, 177, 178). 

The remarkable curariform activity of the Erythrina alkaloids has been discussed in earlier volumes of this series and a review has been published (41). More recent comparison of the activity of dihydro- -erythroidine with standard curare agents such as [Pg.513]

The principal action of the quaternary cinchona alkaloids has been shown to be peripheral (50, 87, 88). The central nervous system is not markedly effected by paralyzing doses, but a transient fall in blood pressure is produced (50, 87, 88, 104). A -Methylquininium chloride has been used on a limited scale in clinical medicine to relieve muscle spasm in certain spastic states (5a, 9, 31). As in the case of curare and the Erythrina alkaloids, synergistic effects are noted between iV-methyl- and iV-ethylquininium chlorides and certain anesthetics and hypnotics (45). 

Finally, it should be mentioned that the curare alkaloids - as is generally known - are quaternary salts and due to their strong hydrophilicity they have to be administered parenterally. In contrast, the Erythrina alkaloids are all tertiary amines and therefore they are able to develop their pharmacological activities upon oral administration. 

Folkers K, Unna K (1939) Erythrina Alkaloids. V. Comparative Curare-like Potencies of Species of the Genus Erythrina. J Am Pharm Assoc 28 1019... 

Many Erythrina alkaloids possess curare-like action and interact with acetylcholine receptors. Extracts of many Erythrina species are used in indigenous medicine, particularly in India. Cocculine and cocculidine nitrates have been reported to show hypotensive action in dogs (Dyke and Quessy, 1981). The insecticidal alkaloid cocculolidine (109) has been isolated from Cocculus trilobus and C. carolinus... 

Benzylisoquinollne alkaloids a group of alkaloids found mainly in members of the poppy family (Papaveraceae). The benzyl substituent on Cl of the isoquinoline radical can enter various secondary cycli-zations through phenol oxidation. The ring structures of the medically important Papaveraceae alkaloids (see), Erythrina alkaloids (see) and the fcisbenzyliso-quinoline Curare alkaloids (see) arise in this way. Biosynthetically, papaverine is derived from 2 molecules of dopa, one being converted to dopamine, the other to 3,4-dihydroxyphenylacetaldehyde. Mannich condensation of these two leads first to norlaudano-sine, which is dehydrated to papaverine (Fig. 1). 

An important factor in stimulating the early structural studies of Erythrina alkaloids during the 1940 s was the discovery of their curariform activity (cf. Craig 1955) this appears to be associated with the spiroamine moiety, and in contrast with the curare alkaloids, which are quaternary salts, the Erythrina alkaloids are all tertiary amines. Many other types of pharmacological activity have also been discovered with Erythrina alkaloids, e.g. sedative, hypotensive, CNS depressing, laxative and diuretic properties. 

The beanlike seeds of the trees and shrubs of the genus Erythrina, a member of the legume family, contain substances that possess curare-like activity. The plants are widely distributed in the tropical and subtropical areas of the American continent, Asia, Africa, and Australia, but apparently they are not used by the natives in the preparation of arrow poisons. Of 105 known species, the seeds from more than 50 have been tested, and all were found to contain alkaloids with curariform properties. Erythroidine, from E. americana, was the first crystalline alkaloid of the group to be isolated. It consists of at least two isomeric alkaloids, a and P-erythroidine both are dextrorotatory. Most experimental and clinical study has centered on the b form because it is more readily obtainable in pure state. P-Erythroidine is a tertiary nitrogenous base. Several hydrogenated derivatives of p-erythroidine have been prepared of these, dihydro-P-erythroidine has been studied most carefully and subjected to clinical trial. Conversion of P-erythroidine into the quaternary metho salt (p-erythroidine methiodide) does not enhance, but rather almost entirely, abolishes its curariform activity this constitutes a notable exception to the rule that conversion of many alkaloids into quaternary metho salts results in the appearance of curare-like action. 

The seeds of Erythrina species are known to contain toxic alkaloids, as well as blood clotting substances, which may be of value in the treatment of thrombosis. The seeds, stem and root bark of some Erythrina species have been used also to stupefy fish, as narcotic, purgative, and diuretic [1,4], while crushed seeds of some have been used as rat poison. All the Erythrina species examined have yielded alkaloids, mostly of the erythrinaline type, having the curare like poisoning action [1,4]. Several of the more common species are used for decorative purposes in gardens and city streets. 

There is no uniform classification for the A. In the literature divisions according to origin (examples Aconitum, Amaryllidaceae, Aspidosperma, cactus, Catharanthus, Cephalotaxus, Cinchona, coca, Corydalis, curare, Dendrobates, ergot, Erythrina, Iboga, Lycopodium, Maytenus, opium, Rauvol-fia, Senecio, Strychnos, tobacco, Vinca alkaloids, salamander, Solanum, Veratrum steroid alkaloids) in addition to divisions according to chemical structure (examples aporphine, benzylisoquinoline, bis-benzylisoquinoline, berberine, carboline, diterpene, inudazole, indole, indolizidine, isoquinoline, lupinane, macrocyclic, morphine, peptide, / -phenyl-ethylamine, piperidine, purine, pyridine, pyrrolidine, pyrrolizidine, quinoline, quinolizidine, quinucli-dine, spermine, spermidine, steroid, terpene, tro-pane, tropolone alkaloids) are used. 

The history of erythrina research begins at the end of the 19 century. During the last two decades of that time extracts from species of Erythrina have been found to exhibit curare-like neuromuscular blocking activities which are caused by alkaloids occurring therein 1-4). 

Between 1940 and 1950 the systematic examination of more than fifty Erythrina species showed that all the alkaloids isolated produce effects similar to curare alkaloids 116, 119), which had been used as adjuvant in surgical anaesthesia (720). 

Folkers K, Major RT (1937) Isolation of Erythroidine, an Alkaloid of Curare Action, from Erythrina americana Mill. J Am Chem Soc 59 1580... 

Alkaloid with curare-like action isolated from several speoieB of Erythrina. Needles from EtOH. M.p. 20A-6°. Sol. CSHCL. Mod. sol. EtOH, Et,0. [a]5 + 248° in EtOH. Readily hyd. Weakly basic. 

Alkaloid with curare-like action isolated from several species of Erythrina. Oryst, from EtOH. M.p. 241-2°. Spar. sol. H,0, CHCI3 and hydr-oxylio solvents, [a] ," -f- 265 2° in EtOH-glycerol. Aq. FeCl, containing drop of HCl... 

Alkaloid with curare-like action isolated from seeds of Erythrina aandwieensie, Deg. and Ery-thrina aubumbrana (Hassk.) Merrill. Cryst. from Et,0-pet. ether. M.p. 103-4°. B.p. 125°/3 9 x 10 mm. Sol. MeOH, EtOH, AcOEt, C H . Mod. sol. EtjO. Prac. insol. pet. eth. JVee base unstable. 

Alkaloid with curare-like action isolated from Erythrina glauea, Willd. Oryst. as hend-hy ate from EtjO-pet. ether. M.p. 170°. [a] 4- 145 5° in EtOH. 

Alkaloid with curare-like action isolated from seeds of Erythrina americana. Mill. M.p. 94 -6°. Sol. HjO, MeOH, EtOH, CHa, C H . Mod. 

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