Alkaloids as drugs

Medical applications of alkaloids have led to the production of drugs and drug components. They can be based on pure natural alkaloids, as in the case of extracts. Purified alkaloids, partially and even totally synthesized compounds based on the natural alkaloid structure, are also used. Chemically modified alkaloids are yet another example. Chemically modifying the structure affects biological activity. The general trend in modern medicine is to develop compounds that are biologically more active than those found in nature. This is achieved in many cases by alkaloid modifications and synthesis. However, natural compounds themselves are very important because they are the basis for artificial drugs. Moreover, alkaloids used as natural products are important 

Atropine-, hyoscine- and hyoscyamine-based drugs are developed on a large scale and they also have a variety of clinical purposes. Atropinol, for example, is based on atropine. This drug contains atropine sulphate. Another example is Buscopan, based on hyoscine. Hyoscyamine is used in transdermal plasters. Bella sanol also contains hyoscyamine. The therapeutic use is similar to that of atropine. At least 50 different products from these alkaloids have been developed and introduced on the pharmaceutical market. 

Drugs based on eserine, galanthamine, nicotine, lobeline and tubocurarine are also prominent. Two examples of drugs containing eserine are Antichohum and Pilo-Eserin. There are at least 20 different products based on this alkaloid. 

Nicotine is used in many products on the pharmaceutical market, for example Nicorette or Nicoderm. At least 20 different products are known to contain nicotine. These drugs are delivered in different forms. One of these is a transdermal plaster. Nicotine chewing gum and tablets are also available. These drugs are used especially to reduce nicotine cravings. 

The drugs that contain lobeline are, for example, Stopsmoke or Lobatox. These products are used for similar purposes as drugs that contain nicotine. 

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A somewhat different perspective is presented in reviews that take as their starting point the toxicity of poisonous forage plants to Hvestock— the factor that led to the discovery of many of the polyhydroxylated alkaloids in the first place. An important review in the current series of volumes adopts this approach. Genera including Astragalus, Oxytropis (the infamous North American locoweeds see Section 3.5.1) and Castanospermum are dealt with in similar reviews, the first of which also elaborates on the development of animal models for human diseases and the resulting exploration of relevant alkaloids as drug candidates. 

This series in heterocychc chemistry is being introduced to collectively make available critically and comprehensively reviewed hterature scattered in various journals as papers and review articles. All sorts of heterocyclic compounds originating from synthesis, natural products, marine products, insects, etc. will be covered. Several heterocyclic compounds play a significant role in maintaining life. Blood constituents hemoglobin and purines, as well as pyrimidines, are constituents of nucleic acid (DNA and RNA). Several amino acids, carbohydrates, vitamins, alkaloids, antibiotics, etc. are also heterocyclic compounds that are essential for life. Heterocyclic compounds are widely used in clinical practice as drugs, but all applications of heterocyclic medicines can not be discussed in detail. In addition to such applications, heterocyclic compounds also find several applications in the plastics industry, in photography as sensitizers and developers, and the in dye industry as dyes, etc. 

Cinchona alkaloids have been used as drugs for the treatment of several diseases. Quinine is very popular as an antimalarial drug against the erythrocyte stage of the parasite [34]. Recently, Shibuya et al. (2003) reported the microbial transformation of four Cinchona alkaloids (quinine, quini-dine, cinchonidine, and cinchonine) by endophytic fungi isolated from Cin-... 

Saponins are glycosylated secondary metabolites that are widely distributed in the Plant Kingdom.3,4 They are a diverse and chemically complex family of compounds that can be divided into three major groups depending on the structure of the aglycone, which may be a steroid, a steroidal alkaloid, or a triterpenoid. These molecules have been proposed to contribute to plant defense.3 6 Saponins are also exploited as drugs and medicines and for a variety of other purposes.4 Despite the considerable commercial interest in this important group of natural products, little is known about their biosynthesis. This is due in part to the complexity of the molecules, and also to the lack of pathway intermediates for biochemical studies. 

Tillequin F. (2007) Rutaceous alkaloids as models for the design of novel antitumor drugs. Phytochem Rev 6 65-79. 

Hydrocodone is an opium analgesic (pain reliever) and antitussive (cough suppressant). It is related in structure to other alkaloids used as drugs, such as morphine and codeine (see Section 8). It increased 20% in number of prescriptions for one year. Its synthesis from codeine is by simple reactions. 

Even (R)-2-methylbutanoic acid of high enantiomeric purity (more than 99%) has been reported as a natural compound in the extract of the steroid alkaloid containing drug Veratrum album L. [40]. 

Isoquinohne alkaloids play an important part in medicine. A number of these alkaloids are available as drugs. Some examples of isoquinohne derivatives with medicinal values are summarized in the following table. In addition to their medicinal uses, isoquinolines are used in the manufacture of dyes, paints and insecticides, and as a solvent for the extraction of resins. 

Atropine and scopolamine, which are obtained from belladonna alkaloids, as well as other synthetic anticholinergic drugs, inhibit the actions of acetylcholine and cholinomimetic drugs at muscarinic receptors in smooth muscles, heart, and exocrine glands. In addition to these peripheral... 

An interesting approach toward the total synthesis of the Stemona alkaloid, (-)-stenine (25), which have been used in Chinese and Japanese folk medicine as insecticides, as drugs for the treatment of respiratory diseases, via spirolactone... 

Biological assays are, of course, necessary in the final stages of evaluation of alkaloid isolates as drugs. Many examples may be found in Section VIII (see Table II). The most economical approach to the screening of large numbers of crude extracts is probably to use in vitro assay on cell cultures (e.g., KB carcinoma), followed by in vivo evaluation, and, finally, isolation of compounds from active fractions (208). 

Grynkiewicz G, Gadzikowska M (2008) Tropane alkaloids as medicinally useful natural products and their synthetic derivatives as new drugs. Pharmacol Rep 60 439 163... 

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