Tropane alkaloids pharmacology

The tropane alkaloids are a well-recognized group of structurally related natural products. Long before elucidation of the structures, the mydriatic and anesthetic action of several compounds was exploited (6). The very extensive literature covering the pharmacological properties of the tropane alkaloids will be considered only briefly in this chapter. Readers with a deeper interest in the subject are referred to other publications (7-14) and to the references given in Section VII. 

Tropane alkaloids, long known to have anticholinergic, antiemetic, parasympatholytic, anesthetic, and many other actions, have been featured in an extremely wide number of pharmacological reports. The section Pharmacology in Chemical Abstracts (Vols. 90-105) lists over 600 articles. To deal in an adequate way with these articles would go far beyond the scope of the present chapter, and interested readers are referred to Chemical Abstracts. Many of the same articles are mentioned in Periodical Reports (9a-9h). Only a few papers (vide infra) will receive comment here. 

A special issue of The Journal of Ethnopharmacology in 1981 (Vol. 3, Nos. 2-3) was devoted to coca and cocaine (98). Several other, more general articles on the pharmacological effects of tropane alkaloids have recently appeared (173-185). 

The relationship between cuscohygrine and the tropane alkaloids, their cooccurrence, and their important pharmacological properties justify the numerous citations of cuscohygrine in the literature. The presence of cuscohygrine has been noted in the following families, genera, and species ... 

The cholinergic hallucinogens all have common chemical constituents that are responsible for their pharmacological effects (Robbers et al. 1996). These are the tropane alkaloids hyoscyamine, scopolamine (or hyoscine), and atropine (figure 9.16). It is scopolamine, and not atropine or hyoscyamine, which primarily produces the central and hallucinogenic effects because it is the only one that passes the blood-brain barrier sufficiently. However, all three have peripheral effects. Datura stramonium contains 0.1-0.65% tropane alkaloids, which is principally... 

Tropane alkaloids, principally hyoscyamine and hyoscine, are also found in two other medicinal plants, scopolia and mandrake, but these plants find little current use. Scopolia (Scopolia carniolica Solanaceae) resembles belladonna in appearance, though it is considerably smaller. Both root and leaf materials have been employed medicinally. The European mandrake (Mandragora officinarum Solanaceae) has a complex history as a hypnotic, a general panacea, and an aphrodisiac. Its collection has been surrounded by much folklore and superstition, in that pulling it from the ground was said to drive its collector mad due to the unearthly shrieks emitted. The roots are frequently forked and are loosely likened to a man or woman. Despite the Doctrine of Signatures, which teaches that the appearance of an object indicates its special properties, from a pharmacological point of view, this plant would be much more efficient as a pain-reliever than as an aphrodisiac. 

Lounasmaa M and Tamminen T (1993) The tropane alkaloids. The Alkaloids, Chemistry and Pharmacology (ed Cordell GA) Vol 44. Academic, San Diego, 1-114. 

Tropane alkaloids are an important class of natural products possessing different and interesting pharmacological activities. Hyoscyamine (atropine in the racemate form), scopolamine, and cocaine are the major representatives of this class. They are commonly found in plant materials, mainly in genera belonging to three families Solanaceae, Erythroxylaceae, and Convolvulaceae. The importance of these compounds requires that there are accurate analytical methods for their determination in plants and in biological matrices. This chapter describes the state-of-the-art of analytical procedures (extraction and analysis) for analyzing tropane alkaloids. 

The family Solanaceae is one of the important and interesting plant families. It may be classified into four groups based on their usefulness and chemical composition of alkaloids contained (1) Nicotiana spp. such as N. tabacum and N. rustica, which provide tobacco and contain nicotiana alkaloids such as nicotine and nomicotine (2) Hyoscyamus, Scopolia, Atropa, and Datura species, which are pharmacologically important and contain tropane alkaloids such as hyocyamine, scopolamine, and tropine (3) Solanum spp., which are sometimes the starting material for production of synthetic steroids for medical uses and which contain solanum alkaloids and (4) Capsicum, Solanum, and Lycoper-sicum species, which serve as foods and are alkaloid-free. 

The tropane alkaloids in Mandragora species are powerful anticholinergic agents and can cause peripheral symptoms (for example blurred vision, dry mouth) and central effects (for example drowsiness, delirium) (15). They can potentiate the effects of synthetic drugs with similar pharmacological activity. 

Subsequent to the appearance of Volume VI of this series, a number of reviews on the tropane alkaloids have appeared, dealing with chemistry (i, 2), biosynthesis and biogenesis (3, 4), and pharmacological activity as a function of structure (5, 6). 

Alkaloids (most alkaloids are pharmacologically active and many are of therapeutic value) Tropane alkaloids Scopolamine, apoatropine and atropine Adsorption Partisil Diethyl ether/ methanol (90 10) plus one per cent diethylamine... 

The biosynthesis of tropane alkaloids has been extensively studied over the last few decades. This is mainly due to the pharmacological importance of compounds such as (-)-hyoscyamine, (-)- scopolamine and (-)-cocaine. An excellent review has been published on that subject by Leete [26]. 

Table 3. Main Pharmacological Properties of Tropane Alkaloids...

I. fuchsioides have indicated the presence of alkaloids, but these have not been identified. It is probable this species contains entheogenic tropane alkaloids (Schultes 1977A Schultes Hofinann 1980), but so far, only content of non-visionary wi-thanolides of obscure pharmacology has been reported (Shemluck 1991). 

Hyoscyamine and its racemic form atropine (extracted from Hyoscyamus niger, Atropa belladonna, and Mandragora officinarum), scopolamine (a co-product of hyoscyamine in Datura plants), cocaine (isolated from Erytroxylon coca), and calystegine (isolated from Solanum tuberosum) are tropane alkaloids that have widespread pharmacological use [38, 39], Atropine, hyoscyamine, and scopolamine... 

The tropane alkaloids are a large important class of natural products which have variety of chemical structures and interesting pharmacological activities. These alkaloids are characteristic secondary metabolites for the families Solanaceae, Convolvulaceae, Erythroxylaceae, Proteaceae, and Rhizophoraceae, and they have been used as chemotaxonomical markers. The intensive investigations in the branch of tropane alkaloid chemistry continue and by the use of modem physical detection techniques, the number of new compounds steadily increases. 

Tropane alkaloids are still of significant interest for the pharmaceutical industry, as well as for pharmacology, toxicology, and phytochemistry, which is evident from the number of articles on the topic which have been published since our previous review [15]. Thus, this chapter will essentially cover the evolution of analytical methods for this class of compounds over the past few years. Calystegines and other polyhydroxylated compounds will not be further discussed herein as they have been thoroughly reviewed by Drager [14, 24]. 

---