Tropane alkaloids

Lec.( 4 )
Tropane alkaloids

Cocaine
Coca or coca leaveshave beendescribed as the dried leaves of Erythroxylumcoca Lamarck , belong to the family (Erythroxylaceae) .
Coca leaves used as a source for cocaine ,In theproccssing of the leaves to cocaine,thefarmersturning the leaves intococa paste which
is easier to transport to a cocaine processing laboratory.
for this purpose are commonplace
Between 100 and 200 kg of dried leaves is needed to make a single
kg of paste, and 2.5 kg of coca paste will yield 1 kg of cocaine.

Coca leaves contain three basic types of alkaloids:
1- Derivarives of ecgonine( cocaine,cinnamylcocaine,alpha, and beta-
truxilline) .
2- Tropine( tropacocaine,valerine ) .
3-Hygrine (hygroline, cuscohygrine )

The composition of the alkaloid mixture in the leaf varies qualitatively
And quantitatively according to the variery of the plant and. to some extent, to the stage of development of the leaves when collected .


Cocaine is an alkaloid obtained from the leaves of Erythroxylum coca andE. .truxillenseand theirvarieties.Much of the alkaloid is actually prepared by semisynthesis from plant_derivedecgonine.

Cocainehas multiple central and peripheral
Nervous system actionsOver most of its effective dose range, it is a psychomotor stimulant with a strong abuse potential .The action responsible for the rewarding property, and hence the abuse liability, is through aprolongation of dopamine in the synapse by blocking the dopamine reuptake mechanism.

Cocaine andCocainehydrochloride as agents of abuse,are
Generally inhaled or sniffed and are rapidly absorbed across the pharyngeal mucosa, resulting in cerebralstimulationand euphoria. In addition, they are injected intravenously and subcutaneously,
Andcocaine free-base issmoked.Inhalation of the vapors of alkaloidal cocaine, knownas "free-basing. " has become a popular practice because of the rapidity of onset and the intensity of the euphoric experience.

Whensmoked the cocaine is absorbed by pulmonary capillaries
ard moves from the lungs to the left side of the heart and then directly to the brain; the effects are perceptible in 7 to l0 seconds. Repeated use results in psychic dependence and tolerance; cocaine is classified as a
Schedule II drugs under the Controlled Subdtances Act.Cocaine served asthe model for a large number of synthetic local anesthetics that have been produced to increase the stability and reduce the toxicity of the natural product. Some of them are vasodilators and are often employed in conjunction with epinephrine. Such compounds are considered in detail in the standard textbooks of medicinal chemistry.


QUINOLINE ALKALOIDS

Alkaloids containing quinoline as their basic nucleus include those obtained from cinchona (Quinine , quinidine , cinchonine, andcinchonidine).
Cinchona and its alkaloids are the only member of this group that are
Therapeutically important at present.
Cinchonine, which is isomeric with cinchonidine, is the parent alkaloid of the quinine series. Quinine and its isomer, quinidine, present 6-methoxycinchonine.

Biosynthesis of Quinoline Alkaloids

Quinine is metabolically derived from the monoterpenoid – tryptophan path way that leads to the corynane-type indole alkaloids.The most distinctive
feature of quinine biosynthesis appears to be cleavage of thebenzopyrrole ring of the tryptophan moiety and rearrangement to form the quinuclidine ring system and then the quinoline moiety. As illustrated in (Fig.9-5, page 156 ).

Cinchona
Cinchona.cinchona bark, or Peruvianbark is the dried bark of the stem or of the rootof Cinchona succirubruPavon et Klotzsch, or its hybrids, known in commerce asredcinchona.
Cinchona contains some 25 closely related alkaloids, the most important of which are quinine, cinchonine, and cinchonidine, and the average yield is 6 to 7%, of which from 1/2 – 2/3 is quinine in the yellow barks. In the red barks, cinchonidine exists in greater proportion.
Cinchona and its alkaloids have been used in the treatment of malaria fever for many years.
Quinine alkaloid is utilized primarily in the preparation of effervescent tonic water. Quinidine is now the principal cinchona alkaloid employed therapeutically.
Overdose of cinchona products result in temporary loss of hearing and in impaired sight.
Ringing in the ears is a symptom of toxicity.
When these symptoms are produced as the result of continuous use of cinchona or of quinine, the condition has been called cinchonism.



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ISOQUINOLINE ALKALOIDS


The isoquinoline alkaloids represent the largest single group of plant alkaloids, and there is great variation in their chemical structurs. Some of the important isoquinoline subgroups are the benzylisoquinolinesrepresented by papaverine and tubocurarine, the benzophenanthridines represented by sanguinarine, the pthalideisoquinolines are represented by hydrastine, the morphinans represented by the opium alkaloids, (Codeine, morphine, thebaine), the protoberberines represented by berberine, and those with the emetine skeleton.

Biosynthesis of Isoquinoline Alkaloids

The Isoquinoline Alkaloids result from the condensation of a phenylethylamine derivative with a phenylacetaldehyde derivative. Both of these moieties are derived from phenylalanine or tyrosine.

Papaver somniferum has a highly useful secondary metabolism that culminates, at least from the therapeutic viewpoint , in morphine.
P. bracteatumLindley, a thebaine producing poppy, and thebaine can be converted to codeine.


Ipecac
Ipecac consists of the dried rhizome and roots of Cephalisipecacuanha
Ipecac in the form of syrup, is used in the treatment of drug overdose and in certain poisonings. It produces emesis through a local irritant effect on the the gastrointestinal mucosa and a central medullary effect by stimulation of the chemoreceptor trigger zone. The usual dose in adults and children older than one year of age is 15 ml, followed by one to two glasses of water and may be repeated once in 20 minutes if emesis does not occur.

Emetine is an alkaloid obtained from ipecac, Emetine hydrochloride is an antiamebic and acts primarily in the intestinal wall and the liver. Also it used as an antiprotozoan, particularly in the treatment of amebic dysentery, It possessed expectorant and emetic properties.

Hydrastis
Hydrastis consists of the dried rhizome and roots of Hydrastiscanadensis L
Three alkaloids have been isolated from hydrastis : ( Hydrastine, berberine, and canadine ). Hydrastineand berberineare used as astringents in inflammation of the mucous membranes.

Sanguinaria
Sanguinariais the dried rhizome ofSanguinaria CanadensisL.
Sanguinariacontains alkaloids including sanguinarine, chelerythrine,protopine, and allocryptopine.
Sanguinariahas stimulating expectorant and emetic properties. Also sanguinariaextract, representing a mixture of the total alkaloids has been incorporated into toothpaste and mouthwash for the prevention of the development of dental plaque and subsequental disease.

Opium
Opium :is the air-dried milky exudate obtained by incising the unripe capsules of Papaver somniferum L. More than 30 different alkaloids have been obtained from opium and its extracts, the most important of these are
Morphine, Codeine, noscapine(narcotine), Papaverine, and Thebaine.

Morphine :is the most important of the opium alkaloids. Morphine is the prototype of opiate analgesic drugs which act at several sites in the central nervous system to produce analgesia.

Codeine :is the most widely used opium alkaloid, codeine and its salts arenarcotic analgesicsandantitussives, they are used assedatives, especiallyinallaying coughs. Although its action is similar to that of morphine, codeine is considerably less toxic and involves much less danger of habit formation.

Heroin
Heroin is formed by the acetylation of morphine,Heroins action is similar but more pronounced than that of morphine, because of its potency and the danger of habit formation.

Papaverine
Papaverineoccurs naturally in opium to the extent of about 1%, Papaverine hydrochlorideis a smooth musclehemiarelaxant. It is used principally for the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias.




Dr. Saad Ali Ihsan
Professor of Medicinal & Aromatic Plants




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