Rauwolfia alkaloids drugs

Most DA (up to 75%) is stored in vesicles like NA. This can be disrupted by the rauwolfia alkaloid, reserpine and by drugs like tetrabenazine. It should be emphasised that these drugs deplete the neurons of amines by stopping their incorporation into... 

The Rauwolfia alkaloid reserpine, due to its strong central component of activity, is excluded from this review, even though it has the peripheral effect of releasing norepinephrine from storage sites where it can be metabolized by monoamine oxidase. This results in neurotransmitter depletion and it appears that good blood pressure control would be achieved by a drug which has this peripheral mechanism but lacks the central component. The Mead-Johnson compound MJ-10459-2 (LXI) shows activity in... 

The primary limiting effect of reserpine is depression. Depletion of central monoamines is believed to be the mechanism for this effect (Heninger et al. 1996 Charney 1998). The depression may occur in a gradual and insidious manner, and the causal association between the drug and depression may be missed (Oates 1996). Rauwolfia alkaloids are contraindicated in anyone with a history of depression, and careful vigilance is required to ensure that they do not induce depression in otherwise normal individuals. Additional side effects are sedation and difficulty with concentration and performing complex mental tasks. 

Drugs that may affect nasal decongestants include beta blockers, furazolidone, guanethidine, methyidopa, MAO inhibitors, rauwolfia alkaloids, tricyclic antidepressants, urinary acidifiers, and urinary alkalinizers. 

Additive - the drugs have the same biochemical mechanism and will react with the target cells as long as receptor sites are available. Examples are the cyclooxygenase inhibitors (prostaglandin synthesis inhibitors) aspirin and acetaminophen (Tylenol ), antihypertensives propanolol and the rauwolfia alkaloids. 

Quinidine is the current drug of choice in the treatment of auricular arrhythmias. The other Cinchona alkaloids, the cryptopine-like compounds, sparteine and related substances, and the Rauwolfia alkaloids are primarily of interest in these arrhythmias. Quinidine or digitalis occasionally prove of therapeutic merit in preventing the ventricular arrhythmias. 

It is, however, interesting to observe that a good number of sympathomimetics in fact do not really mimic the actions of noradrenaline or adrenaline at the effector receptor. They merely induce the release of noradrenaline from the sympathetic postganglionic adrenergic nerves. Such sympathomimetics which exert their action indirectly are comparatively less effective in patients treated with noradrenaline depleting drugs, for instance, the rauwolfia alkaloids, or other adrenergic neuron blockers. 

Central excitation and possibly hypertension can occur if rauwolfia alkaloids are given to patients already taking an MAOI, but is less likely if the rauwolfia alkaloid is given first. Theoretically additive blood-pressure lowering effects are also a possibility. The use of drugs that have the potential to cause depression, such as the rauwolfia alkaloids or tetrabenazine, is generally contraindicated in patients needing treatment for depression. 

Reserpine therapeutically the most important Rauwolfia alkaloid. M, 608.9, m.p. 265 C, (oj -123° (CHQj). Hydrolysis of R. with alcoholic KOH produces reserpinic add (structurally similar to yohimbine), trihydroxybenzoic add and methanol. R. is found widely in Ae genus Rauwolfia and is responsible for the sedative properties of these plants. After a latent period, R. causes long lasting sedation, with decrease of blood pressure and decreased pulse rate. It is used as a powerful neuroleptic drug in psychiatry. 

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. 

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. 

Antihypertensive agents, substances that lower high blood pressure, are an important subclass of cardiovascular agents. Reserpine, an indole alkaloid obtained from the Rauwolfia plant, was the first successful drug to... 

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. 

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. 

In 1918 the traditional Indian remedy rauwolfia was reported to be useful in the treatment of hypertension. Reexamination of this material led to the isolation of reserpine (28 R1 = Me, R2 = 3,4,5-trimethoxybenzoyl) which was shown in 1952 to have hypotensive and tranquilizing effects. Other alkaloids such as deserpidine (28 R1 = H, R2 = 3,4,5-trimethoxybenzoyl) and rescinnamine (28 R1 = Me, R2 = 3,4,5-trimethoxycinnamoyl) were later isolated. They are useful when alternative, more potent drugs are not well tolerated. 

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