Pharmacology, ajmaline alkaloids

Attention should also be drawn to recent publications on the isolation of a new hypotensive factor from the roots of R. serpentina (120). In these publications, the separation of the crude alkaloids from fresh undried R. serpentina roots into four alkaloidal complexes is reported. The first three fractions have been named resajmaline, ajmalexine, and serpajmaline, respectively. The serpajmaline fraction is said to be therapeutically active and also is claimed to contain serpentinine, serpentine, ajmaline, and two unknown substances, one of which is probably reserpiline. This fraction is said also to be free from reserpine and to be much more potent in its hypotensive activity than reserpine, but to lack reserpine s sedative and central nervous depressant action. However, a later pharmacological investigation of an authentic water-soluble serpajmaline fraction (alkaloids present as salts) demonstrated that the type of antihypertensive activity observed closely resembles that of serpentine and serpentinine (121). This conclusion receives support from a chemical study of this fraction in which serpentinine, ajmaline, and tetraphyllicine were obtained in a pure state (121). 

Only a few new pharmacological effects have been indicated for the alkaloids of the ajmaline group. Most of diem concern symaline (17) itself, wdiich has been known since 1959 (207) and is used in the treatment of cardiac arrhythmia (20S, 209). 

There are a large number of alkaloids that contain the quinuclidine nucleus such as the sarpagine, ajmaline and cinchona families. The quinuclidines 1-3 have been used for the synthesis of such alkaloids. They have pharmacological activities. Thus, several reports have highlighted the potential of chiral hydroxylated quinuclidines in propping the active site of muscarinic receptors. Substituted quinuclidines may provide selective Vaughan Williams class 111 antiarrhythmic effects. " ... 

Rauwolfia serpentina Benth. is the source of several related alkaloids. Ajmaline, ajmalicine, ajmalinine, serpentine, serpentinine, isoajmaline, and neoajmaline have been identified. Ajmaline and serpentine have been given provisional structural formulas (81, 82). Other members of the Apocynaceae yield alkaloids of similar properties. Although Rauwolfia preparations have been used in Ayurvedic medicine for hypertension, there appear no indications that they have been used in clinical cardiac arrhythmia. Yet, incomplete pharmacologic studies indicate properties for these alkaloids which should prompt additional studies toward their possible use in auricular fibrillation. 

During the recent decades, attempts were made to detect novel biological and pharmacological activities of alkaloids from the genus Rauvolfia. The results demonstrated that ajmaline and derivatives interact with ion... 

Some R. a. have valuable pharmacological properties. They may act centrally (e.g. see Reserpine) or peripherally (e g. see Yohimbine, Ajmaline). In addition to the pure alkaloids or their synthetic analogs, extracts of the drug Radix Rauwolfiae and combination preparations are also used. The drug has been known since early times in Indian folk medicine, and its systematic investigation began in 1930. 

This highly unsaturated indole alkaloid (CVI) which, like ajmaline, incorporates skeletal pattern XXI, has similar pharmacological properties to ajmaline, producing a brief hypotension [1136,1139-1142] which is due to a diminished cardiac output resulting from its quinidine-like action on the heart [1105, 1106, 1108-1110, 1143, 1144]. However, the unpredictable frequency of response and untoward side effects militate against clinical application of serpentine [1145] or its synthetic analogues [1146]. 

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