Rauwolfia serpentina

Rating programs Rational design Rational drug discovery Rauwolfia serpentina Rauwolscine [131-03-3]... 

Neuronal Norepinephrine Depleting Agents. Reserpine (Table 6) is the most active alkaloid derived from Rauwolfia serpentina. The principal antihypertensive mechanism of action primarily results from depletion of norepinephrine from peripheral sympathetic nerves and the brain adrenergic neurons. The result is a drastic decrease in the amount of norepinephrine released from these neurons, leading to decrease in vascular tone and lowering of blood pressure. Reserpine also depletes other transmitters including epinephrine, serotonin [50-67-9] dopamine [51-61-6] ... 

Many alkaloids have pronounced biological properties, and a substantial number of the pharmaceutical agents used today are derived from naturally occurring amines. As a few examples, morphine, an analgesic agent, is obtained from the opium poppy Papaver somnifemm. Cocaine, both an anesthetic and a central nervous system stimulant, is obtained front the coca bush Erythroxylon coca, endemic to upland rain forest areas of Colombia, Ecuador, Peru, Bolivia, and western Brazil. Reserpine, a tranquilizer and antihypertensive, comes from powdered roots of the semitropical plant Rauwolfia serpentina. Ephedrine, a bronchodilator and decongestant, is obtained front the Chinese plant Ephedra sinica. 

By extraction from the pulverized roots of Rauwolfia serpentina (L.) Beuth. 

In 1952 reserpine, an alkaloid extract from the Indian snakewort plant, Rauwolfia serpentina, which had been used in that country to treat madness , was first tried in schizophrenia. The beneficial impact on patients and the hospital wards was dramatic, as was that a year later of chlorpromazine, a phenothiazine derivative and haloperidol, a butyrophenone. These latter two drugs and closely related derivatives remained the mainstay of therapy for almost 40 years. 

Reserpine A drug extracted from Rauwolfia serpentina which was once clinically used in the treatment of essential hypertension and schizophrenia. 

Salutaridinol 7-0-acetyltransferase catalyzes the conversion of the phenanthrene alkaloid salutaridinol to salutaridinol-7-Oacetate, the immediate precursor of thebaine along the morphine biosynthetic pathway in P. somniferum (Fig. 10.7).26 Acetyl CoA-dependent acetyltransferases have an important role in plant alkaloid metabolism. They are involved in the synthesis of monoterpenoid indole alkaloids in medicinal plant species such as Rauwolfia serpentina. In this plant, the enzyme vinorine synthase transfers an acetyl group from acetyl CoA to 16-epi-vellosimine to form vinorine. This acetyl transfer is accompanied by a concomitant skeletal rearrangement from the sarpagan- to the ajmalan-type (reviewed in2). An acetyl CoA-dependent acetyltransferase also participates in vindoline biosynthesis in Catharanthus roseus, the source of the chemotherapeutic dimeric indole alkaloid vinblastine (reviewed in2). Acetyl CoA deacetylvindoline 4-O-acetyltransferase catalyzes the last step in vindoline biosynthesis. A cDNA encoding acetyl CoA deacetylvindoline 4-0-acetyltransferase was recently successfully isolated.27... 

Other plants known to contain psychoactive compounds include hellebore, which was used for centuries in Europe to treat mania, violent temper, mental retardation and epilepsy. However, a drug of major importance in modern psychopharmacology arose from the discovery by medicinal chemists of the alkaloids of Rauwolfia serpentina, a root which had been used in the Indian subcontinent for centuries, not only for the treatment of snake bite but also for alleviating "insanity". Understandably, the mechanism of action of reserpine, the alkaloid purified from Rauwolfia serpentina, helped to lay the basis to psychopharmacology by demonstrating how the depletion of central and peripheral stores of biogenic amines was correlated with a reduction in blood pressure and tranquillization. 

Yohimbine Yohimbine is methyl ether ( )-2a-hydroxyyohimban-la-carboxylic acid (12.2.16). It is isolated from the plants Corynanthe johimbe and Rauwolfia serpentina [60,61], It is also synthesized [62-66],... 

Figure 9. The devil s-pepper genus contains L-tryptophan-derived alkaloids. Rauwolfia serpentina appears on flowers (Photo T. Aniszewski).

Since the main clinical use for antisympathotonics is in the treatment of essential hypertension, such drugs will be discussed in Chapter 20 in more detail. The alkaloid reserpine from Rauwolfia serpentina was the first drug used clinically to reduce sympathetic tone. Reserpine reduce the ability of storage and release of various transmitters (adrenaline, noradrenaline, serotonine and dopamine) by an irreversible destruction of the axonal vesicle membranes. The duration of the reserpine effect is actually determined by the de novo synthesis of these structure. Beside various central side effects like sedation, depression, lassitude and nightmares the pattern of unwanted effects of reserpine is determined by the shift of the autonomic balance towards the parasympathetic branch myosis, congested nostrils, an altered saliva production, increased gastric acid production, bardycardia and diarrhea. As a consequence of the inhibition of central dopamine release, reserpine infrequently shows Parkinson-like disturbances of the extrapyramidal system. 

Rauwolfia serpentina L. Boith., Gentianales and Corynanthe yohimbe K, Schum., Rubiales, Ang. from S Asia... 

Following the passage of the FD C Act, FDA was authorized to permit NDAs for new drugs, but the agency could not approve them affirmatively (see Section 505 of the FD C Act). One such NDA was for the botanical rauwolfia Rauwolfia serpentina), first marketed in the United States in 1953. Used in India for centuries, root of rauwolfia was sold in the United States as a treatment for hypertension. More than a dozen NDAs were subsequently recorded for the drug, all of which were discontinued by 1982, as better antihypertensives came to market (Table 1). 

Table 1 NDAs for Rauwolfia serpentina (discontinued before January 1, 1982)...

Reserpine, an alkaloid extracted from the roots of an Indian plant, Rauwolfia serpentina, was one of the first effective drugs used on a large scale in the treatment of hypertension. At present, it is rarely used owing to its adverse effects. 

Reserpine is a raulwolfia alkaloid isolated from the roots of the plant Rauwolfia Serpentina. It is used for the treatment of mild essential hypertension or psychosis. 

Further variants on the terpenoid indole alkaloid skeleton (Figure 6.82) are found in ibogaine from Tabemanthe iboga, vincamine from Vinca minor, and ajmaline from Rauwolfia serpentina. Ibogaine is simply a C9 Iboga type alkaloid, but is of interest as an experimental drug to treat heroin addiction. In a number of European countries, vincamine is used clinically as a vasodilator to increase cerebral blood flow in cases of senility, and ajmaline for cardiac arrhythmias. Ajmaline... 

Ajmalicine (see rauwolfia, page 353) is present in the roots of Catharanthus roseus at a level of about 0.4%, and this plant is used as a commercial source in addition to Rauwolfia serpentina. 

Stockigt J (1995) Biosynthesis in Rauwolfia serpentina modern aspects of an old medicinal plant. The Alkaloids, Chemistry and Pharmacology (ed Cordell GA) Vol 47. Academic, San Diego, pp 115-172. 

Rauwolfia serpentina Benth, which derives its name from Leonhart Rauwolf, a 16th century botanist, and its serpentine root (Figure 56.1), has long been used in India for a variety of ailments. The discovery of its tranquilizing action, particularly in lowering the blood pressure, led to its introduction into Western medicine. The Rauwolfia alkaloids are derived from a family of tropical and semitropical plants related to oleander and periwinkle. They vary from small shrubs to tall trees. The important species from which the alkaloids are derived include Rauwolfia serpentina (Ophioxylon serpentinum or Indian snakeroot), R. micrantha, R. vomitoria, and R. hirsuta (Canescens heterophylla). 

FIGURE 56.1 A flowering Rauwolfia serpentina plant. Note the serpentine root from which the plant obtains... 

This book shows how Indians used Rauwolfia serpentina to reduce blood pressure and as an antipsychotic, but also shows that it contains reserpine, which depletes norepinephrine in the periphery bringing about its antihypertensive effects and depletes dopamine in the mesocortical system causing tranquility. 

Reserpine, an alkaloid, and the active ingredient of Rauwolfia serpentina, the Indian snakeroot, was the basis of the first major tranquilizer. Reserpine was used in the treatment of snake bites, high blood pressure, and... 

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