Alkaloids reserpine

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... 

Figure 4.60 shows a synthesis map for various starting materials for the synthesis of the alkaloid reserpine. Metrics for 10 plans are summarized in Table 4.27. The Liao and Stork plans are the best performers overall, however the Pearlman plan has the highest atom... 

Some indolo[2..w/]c iiinolixidines undergo easy acid-catalyzed epimerization <1998H(50)243>. For instance, the alkaloid reserpine equilibrates to a mixture of starting material and its 3-epimer, isoreserpine, under acid or basic catalysis (Equation 6). A controlled epimerization of this type has been employed as the key step in a total synthesis of ( )-tacamonine <1998T157>. 

Reserpine and Related Alkaloids. Rauwolfia alkaloid reserpine (109) and a... 

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... 

In the sympathetic nervous system there is the possibility to reduce the release of noradrenaline. The alkaloid reserpine is known to interfere with the ability of the postganglionic sympathetic nerves to store noradrenaline. This results in a reduction of the sympathetic tone which is a useful measure in the treatment of essential hypertension. These type of drugs are classified as antisympathotonics. 

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. 

The Rauwolfla alkaloid reserpine was originally used as a neuroleptic/antipsychotic agent. It was then discovered to be an effective antihypertensive agent. Reserpine causes depletion of the noradrenaline stores in peripheral postganglionic sympathetic neurons. In addition it causes depletion of noradrenalin in central nervous structures involved in the regulation of blood pressure. 

N.A. Rauvolfia serpentina (L.) Benth. Indole alkaloids, reserpine, rescinnamine, ajmaline, yohimbine.99 Regulate hearbeat, treat high blood pressure and anxiety. Sedative and depressant effect on sympathetic nervous system. 

The alkaloid reserpine [50-55-5], which is isolated from the roots of Raum/fta serpentina T., contains a gallate trimethyl ether moiety. Reserpine is used as an antihypertensive and a tranquilizer. A vinylogue of reserpine, rescinnamine [24815-24-5], is also an antihypersensitive (75). Methoxsalen [298-81-7] (8-methoxypsoralen 7H-9-methoxy-furo[3,2-[Pg.379]

The oxidation of primary and secondary alcohols by stable organic nitroxyl radicals has been reviewed.111 The kinetics of reactions of alkanes and arenes with peroxynitrous acid suggest the participation of the same active oxidizing species in both gas and aqueous phase HOONO or its decomposition product OONO. 112 The oxidation of the alkaloids reserpine and rescinnamine by nitric acid has been studied.113... 

Reserpine. As mentioned earlier, the Rauwolfia alkaloid reserpine is noted for its ability to deplete aromatic biogenic amines in nervous tissue of mammals and insects. One of the more remarkable effects of reserpine in humans is to render individuals indifferent to environmental stimuli. Reserpine appears to have a similar effect on insects, although information is still relatively scanty. In the cockroach, Periplaneta americana, reserpine at 50 vg/g causes strong and long-lasting depletion of the aromatic biogenic amines dopamine, octopamine, and 5-hydroxytryptamine (24). Numerous authors have noted that reserpine has tranquilizing effects on insects, e.g., the ant Formica rufa (30) and . americana (24,31). 

After deglucosylation, the pathway proceeds through a 4,21-Dehydrogeissoschizine derivative to ajmalicine (an a-Blocking spasmolytic agent, used for tinnitus and cranial trauma with an ergot derivative). If cyclization occurs between C-17 and C-18, the yohimbine nucleus is produced, whose derivatives include the Rauvolfia alkaloids reserpine and resdnnamine (antihypertensive activity). Ajmaline, formerly used as an antiarrythmic, also occurs in Rauvolfia species, and several of the enzymes in the pathway have been isolated. Recent considerations suggest that the C-16-C-5 bond may be formed before the N-4-C-21 bond (Fig. 38). 

Easily prepared from glycols, enones have been investigated as dienophiles. They react with butadiene under Lewis acid catalysis to form chiral cyclohexenes used in the synthesis of compactin analogs [353]. Levoglucosenone has been used in a Diels-Alder reaction with acetoxy-butadiene to construct a part of the indole alkaloid reserpine [354], and in synthetic studies toward tetrodotoxin [355]. Analogs of the anthracycline rhodomycinone have been similarly prepared [356]. [4 + 2]-Cycloaddition of the same enone with silyloxydiene allowed the creation of the fused ring system present in actinobolin [357]. 

Isobe, M, Fukami, N, Nishikawa, T, Goto, T, Synthesis of chiral cyclohexanes from levoglucosenone and its application to an indole alkaloid reserpine, Heterocydes, 25, 521-532, 1987. 

Q,C,atropine, acridine.ephe-drine,opium alkaloids,reserpine,strychnine, yohimbine Separation on styrene-divinyl benzene polymer (Table 8.4) - Hitachi gel 3010, 10 pm 220x4.6 ACN-0.02M NH,0H(3 2) ACN-0.02M tetrabutyl-ammoniumhydroxide (3 7), (3 2) 44... 

Alstonine, alstoniline, cillastonine and echitamine Alkaloid, reserpine,... 

Furthermore, the rauwolfia alkaloids (reserpine and others), which also began to be used at that time in psychiatry (and as antihypertensives see Chapter 10), were found to be potent depletors of brain NE and 5-HT in animals. These and additional findings over the next decade led to the (mono)amine hypothesis of mental disorders. The DA hypothesis of schizophrenia is currently the one with the most supportive evidence. 

The roots of Rauwolfla serpentina, a climbing shrub indigenous to India, and named after the German botanist Rauwolf, contains an alkaloid Reserpine which was reported to possess both tranquilizing and hypotensive properties. 

In the history of ethnopharmacology, a most significant event was the isolation and clinical application of the alkaloid reserpine from Rauwolfia spp, a plant that had been used for millennia in the Ayurvedic tradition to treat "madness". Although reserpine had clearly demonstrated antipsychotic efficacy, it was soon replaced by the first synthetic antipsychotic, chlorpromazine, which proved more effective, had fewer side-effects and was relatively inexpensive to manufacture [44]. Exhibit 4 provides overviews for representative studies on natural products with putative anti-psychotic effects. 

This cleavage has also been extended to indole alkaloids (reserpine) as shown in equation... 

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