Drugs Containing Alkaloids

Chapter 15

Drugs Containing Alkaloids

INTRODUCTION

• One of the largest groups of chemicals produced by plants is the alkaloids. Many of these metabolic by-products are derived from amino acids and include an enormous number of bitter, nitrogenous compounds. More than 10,000 different alkaloids have been discovered in species from over 300 plant families. Alkaloids often contain one or more rings of carbon atoms, usually with a nitrogen atom in the ring. The position of the nitrogen atom in the carbon ring varies with different alkaloids and with different plant families. In some alkaloids, such as mescaline, the nitrogen atom is not within a carbon ring. In fact, it is the precise position of the nitrogen atom that affects the properties of these alkaloids. These compounds are renowned for their potent pharmacological activities. Whilst tiny amounts of some can immobilize an elephant or a rhinoceros, others have important clinical use, such as analgesics, antimalarial, antispasmodics, for pupil dilation, treatment of hypertension, mental disorders and tumours.

• They are all nitrogen heterocycles which occur mainly in plants as their salts of common carboxylic acids, such as citric, lactic, oxalic, acetic, maleic and tartaric acids as well as fumaric, benzoic, aconitic and veratric acids. Their amine character produce an alkaline solution in water and hence the origin of their name—alkaloids.

• Although they undoubtedly existed long before humans, some alkaloids have remarkable structural similarities with neurotransmitters in the central nervous system (CNS) of humans, including dopamine, serotonin and acetylcholine. The amazing effect of these alkaloids on humans has led to the development of powerful painkiller medications, spiritual drugs, and serious addictions by people who are ignorant of the properties of these powerful chemicals.

 DEFINITION

• An alkaloid is a nitrogenous organic molecule that has a pharmacological effect on humans and animals. They are a class of compounds which typically contain nitrogen and have complex ring structures. They occur naturally in seed bearing plants and are found in berries, bark, fruit, roots and leaves. Often, they are bases which have some physiological effect. The name derives from the word alkaline; originally, the term was used to describe any nitrogen-containing base (an amine in modern terms). Alkaloids are found as secondary metabolites in plants (e.g., in Vinca and Datura), animals (e.g., in shellfish) and fungi, and can be extracted from their sources by treatment with acids (usually hydrochloric acid or sulphuric acid, though organic acids, such as maleic acid and citric acid are sometimes used).

• Usually, alkaloids are derivatives from amino acids. Even though many alkaloids are poisonous (e.g., strychnine or coniine), some are used in medicine as analgesics (pain relievers) or anaesthetics, particularly morphine and codeine. Most alkaloids have a very bitter taste.

 HISTORY

• Evidence suggests that alkaloids have been used by humanity for thousands of years. The first civilizations to use them were probably the ancient Sumarians and Egyptians. However, it was not until the early nineteenth century that these compounds were reproducibly isolated and analysed. Advances in analytical separation techniques, such as chromatography and mass spectroscopy, led to the elucidation of the chemical structure of alkaloids. The term for these compounds is thought to have originated from the fact that the alkaloid, morphine, had similar properties to basic salts derived from the alkali ashes of plants thus, it was called a vegetable alkali or alkaloid. Since the first alkaloids were isolated, thousands more have. been identified and classified.

• Prior to approximately 300 years ago, malaria was the scourge of Europe, likely having been introduced through the Middle East. Malaria is caused by protozoa of the genusPlasmodium, contained as spores in the gut of the Anopheles mosquito, which then spreads the spores to humans when it bites. As the Spanish and Portuguese explorers began to colonize South America, they discovered a cure for malaria known to the native Indians. This was the bark of the Cinchona trees. The use of Cinchona bark to treat malaria was first reported in Europe in 1633, and the first bark reached Rome about 12 years later. Teas made from the bark cured people suffering from malaria, one of the major scourges in Europe at that time, and the bark was known as Jesuit’s bark. Because of the philosophical differences between Protestants and Catholics, many Protestants refused to be treated with the bark. One of the most prominent Protestants of the time, Oliver Cromwell, reportedly died of malaria because of this stubbornness.

• The French apothecary Derosne probably isolated the alkaloid afterwards known as narcotine in 1803 and the Hanoverian apothecary Serturner further investigated opium and isolated morphine (1806 and 1816). Morphine is the principal alkaloid and was first isolated between 1803 and 1806. It was widely used for pain relief beginning in the 1830s, but was also recognized as being addictive. Isolation of other alkaloids, particularly by Pelletier and Caventou, rapidly followed: strychnine (1817), emetine (1817), brucine (1819), piperine (1819), caffeine (1819), quinine (1820), colchicine (1820) and conine (1826). Coniine was the first alkaloid to have its structure established and to be synthesized, but for others, such as colchicine, it was well over a century before the structures were finally elucidated. In the second half of the twentieth century alkaloids featured strongly in the search for plant drugs with anticancer activity. A notable success was the introduction of Catharanthus alkaloids and paclitaxel into medicine and there is much current interest in other alkaloids having anticancer properties as well as those exhibiting antiaging and antiviral possibilities.

CLASSIFICATION

Alkaloids are generally classified by their common molecular precursors, based on the biological pathway used to construct the molecule. From a structural point of view, alkaloids are divided according to their shapes and origins. There are three main types of alkaloids: 

• true alkaloids 

• protoalkaloids, and 

• pseudoalkaloids. True alkaloids and protoalkaloids are derived from amino acids, whereas pseudoalkaloids are not derived from these compounds.

True Alkaloids

• True alkaloids derive from amino acid, and they share a heterocyclic ring with nitrogen. These alkaloids are highly reactive substances with biological activity even in low doses. All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid. True alkaloids form water-soluble salts. Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants 

• in the free state, 

• as salts and 

• as N-oxides. These alkaloids occur in a limited number of species and families and are those compounds in which decarboxylated amino acids are condensed with a nonnitrogenous structural moiety. The primary precursors of true alkaloids are such amino acids as L-ornithine, L-lysine, L-phenylalanine/Ltyrosine, L-tryptophan and L-histidine. Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine, dopamine and morphine.

Protoalkaloids

• Protoalkaloids are compounds, in which the N atom derived from an amino acid is not a part of the heterocyclic. Such kinds of alkaloid include compounds derived from L-tyrosine and L-tryptophan. Protoalkaloids are those with a closed ring, being perfect but structurally simple alkaloids. They form a minority of all alkaloids. Hordenine, mescaline and yohimbine are good examples of these kinds of alkaloid. Chini et al. have found new alkaloids, stachydrine and 4-hydroxystachydrine, derived from Boscia angustifolia, a plant belonging to the Capparidacea family. These alkaloids have a pyrroline nucleus and are basic alkaloids in the genus Boscia. The species from this genus have been used in folk medicine in East and South Africa. Boscia angustifolia is used for the treatment of mental illness, and occasionally to combat pain and neuralgia.

Pseudoalkaloids

• Pseudoalkaloids are compounds, the basic carbon skeletons of which are not derived from amino acids. In reality, pseudoalkaloids are connected with amino acid pathways. They are derived from the precursors or post-cursors (derivatives the indegradation process) of amino acids. They can also result from the amination and trans-amination reactions of the different pathways connected with precursors or post-cursors of amino acids.

• These alkaloids can also be derived from nonaminoacid precursors. The N atom is inserted into the molecule at a relatively late stage, for example, in the case of steroidal or terpenoid skeletons. Certainly, the N atom can also be donated by an amino acid source across a trans-amination reaction, if there is a suitable aldehyde or ketone. Pseudoalkaloids can be acetate and phenylalanine derived or terpenoid, as well as steroidal alkaloids. Examples of pseudoalkaloids include such compounds as coniine, capsaicin, ephedrine, solanidine, caffeine and theobromine.

• Alkaloids are mainly divided into two categories on the basis of their chemical structure, that is, heterocyclic rings

Atypical alkaloids

• These are also known as nonheterocyclic alkaloids and contain nitrogen in aliphatic chain.

Typical alkaloids

• These are also known as heterocyclic alkaloids and contain nitrogen in heterocyclic ring system.

• The interrelationship between different ways of classifications can be summarized 

OCCURRENCE IN NATURE

• Alkaloids are substances very well known for their biological activity at the beginning of world civilization. They were used in shamanism, in traditional herbal medicine for the cure of diseases and in weapons as toxins during tribal wars and during hunting. They also had, and still have, socio-cultural and personal significance in ethnobotany. Moreover, they have been and continue to be the object of human interest concerning new possibilities for their safe utilization and ensuing health benefits. Of all secondary compounds, historically and contemporaneously, only alkaloids are molecules of natural origin with highly important benefits and diagnostic uses. They can be characterized as the most useful and also the most dangerous products of nature.

• Alkaloids are most abundant in higher plants. At least 25% of higher plants contain these molecules. In effect, this means that on average; at least one in fourth plants contains some alkaloids. In reality, it is not impossible that alkaloids occur more commonly. Using the latest equipment and technology, such slight traces of alkaloids may be detected (e.g., less than l0 gigagrams per kg of plant mass) that these have no real influence on biological receptors and activity. Generally, these species are not considered as alkaloid species. Hegnauer has defined alkaloid plants as those species which contain more than 0.0l% of alkaloids. This is right from the point of view of the classification. From the genetic point of view, and the genetic mechanism of alkaloid synthesis, it is a real limitation. Paying attention to slight traces of alkaloids in plants, we see the members of the plant family which are relatives. They have a genetically determined alkaloid mechanism with a species expression. Moreover, this expression is also on the hybrid level.

• The distribution of alkaloids in nature is restricted to some specific plants, animals or lower plants. The pattern of distribution of compound and its pharmacological activity has a great role in chemotaxonomical classification. Alkaloids are chiefly found to be distributed in angiosperms and to some extent in lower plants (mosses, liverworts) and animals. Nearly about 47–50% of various bacterial species also contain alkaloids, for example, pyocyanine from Pseudomonas aeruginosa. Alkaloids are commonly found in the families like, Chenopodiaceae, Lauraceae, Burseraceae, Neisseriaceae, Ranunculaceae, Papaveraceae, Fumariaceae, Leguminosae, Papilionaceous, Rutaceae, Apocynaceae, Loganiaceae, Rubiaceae, Boraginaceae, Convolvulaceae, Solanaceae, Campanulaceae, Compositae, etc. They may be present in any part of the plant like, roots (reserpine from Rauwolfia), aerial parts like (Ephedra), barks (quinine from cinchona), leaves (Cocaine from Coca), seeds (caffeine from Coca seeds) or even in entire plant (vinblastin from Vinca). 300 alkaloids belonging to more than 24 classes are reported to occur in the skins of amphibians.

PROPERTIES

• Although numerous alkaloids exist, they have similar properties when separated. In general, they are colourless, crystalline solids which are basic, have a ring structure, and have definite melting points. They are also derived from plants and have a bitter taste. However, some exceptions are known. For instance, some alkaloids are not basic, and others are brightly coloured (betanidine, beriberine, sanguinarine) or liquid (nicotine). Other alkaloids are produced synthetically. Most alkaloids are also chiral molecules which mean they have nonsuperimposable mirror images. This results in isomers that have different chemical properties. For example, one isomer may have a physiological function while the other does not.

• Generally free bases of alkaloids are soluble in organic solvents and insoluble in water, whereas alkaloidal salts are soluble in water and partially soluble in organic solvents. For example, strychnine hydrochloride is much more soluble in water than strychnine as a base

EXTRACTION

• The extraction of alkaloids is based on their basic character and solubility profiles. Generally, alkaloids are extracted mainly using two methods.

Method A

• The powdered material that contains alkaloidal salts is moistened with alkaline substances like sodium bicarbonate, ammonia, calcium hydroxide, etc., which combines with acids, tannins and other phenolic substances and sets free the alkaloids bases. Extraction is then carried out with organic solvents such as ether or petroleum spirit. The concentrated organic liquid is then shaken with aqueous acid and allowed to separate. Alkaloid salts will be present in aqueous liquid, while many impurities remain behind in the organic liquid.

Method B

• The collected powdered material is extracted with water or aqueous alcohol containing dilute acid. Chloroform or other organic solvents are added and shaken to remove the pigments and other unwanted materials. The free alkaloids are then precipitated by the addition of excess alkalis like, sodium bicarbonate or ammonia and separated by filtration or by extraction with organic solvents.

• Volatile liquid alkaloids (nicotine and coniine) are isolated by distillation. The powdered material that contains alkaloids is extracted with water and the aqueous extract is made alkaline with sodium carbonate or ammonia and the alkaloid is distilled off in steam. This could be collected and purified. 

 CHEMICAL TESTS

• The chemical tests are performed from neutral or slightly acidic solution of drug. 

Dragen Dorff’s Test 

• Drug solution + Dragendroff’s reagent (Potassium Bismuth Iodide), formation of Orangish red colour.

Mayer’s Test 

• Drug solution + few drops of Mayer’s reagent (potassium mercuric iodide), formation of creamy-white precipitant.

Hager’s Test 

• Drug solution + few drops of Hagers reagent (Saturated aq. Solution of Picric acid), formation of crystalline yellow precipitate.

Wagner’s Test 

• Drug solution + few drops of Wagner’s reagent (dilute Iodine solution), formulation of reddish-brown precipitate.

Tannic Acid 

• Test Drug solution + few drops of tannic acid solution, formation of buff coloured precipitate.

Ammonia Reineckate 

• Test Drug solution + slightly acidified (HCl) saturated solution of ammonia reineckate, formation of pink flocculent precipitate.

TROPANE ALKALOIDS

• The tropane alkaloids, which have the 8-azabicyclo octane nucleus, are commonly found in plants of three families, the Solanaceae, Erythroxylaceae and Convolvulaceae families. Tropane alkaloids are tropene derivatives. Tropane ring is composed of pyrrolidine and piperidine rings. Tropane is 3-hydroxy tropene. There are two stereoisomers of tropene, tropine and pseudo tropine. They are esters combined with acids. These esters of tropic acid could be detected by vitali– morin reaction. The acids present are tropic acid in atropine and atropic acid formed by the loss of water from tropic acid in apoatropine. Other organic acids like tiglic acid, acetic acid, isobutyric acid and isovaleric acid are also present.

• The alkaloids isolated from plants of these families, while having several legitimate medicinal uses, are probably best known for their toxic properties. This can be a major problem since the plants produce very attractive berries which are tempting to small children. As few as three berries of henbane (Hyoscyamus niger) or deadly nightshade (Atropa belladonna) can cause death in infants. Many of the plants in the Solanaceae family contain tropane alkaloids, which are responsible for the toxic effects of the plants. Cleopatra is reputed to have tested the effects of henbane and deadly nightshade on her slaves to investigate the possibility of using these extracts to commit suicide (she found the toxic effects too painful). The wives of the Roman emperors, Augustus and Claudius, used deadly nightshade to murder large numbers of Romans. The mandrake (Mandragora officinarum) was reputed to possess aphrodisiac properties and was prized for these properties. However, the roots also contain large quantities of the tropane alkaloid hyoscine (scopolamine), making the plant highly toxic. 

BELLADONNA

Synonyms 

• Belladonna herb; Belladonna leaf; Deadly night shade leaves; Banewort; Death’s herb, Dwale; Poison black cherry; Folia belladonnae.

Biological Source 

• Belladonna consists of dried leaves and flowering tops of Atropa belladonna Linn. (European Belladonna), belonging to family Solanaceae. It contains about 0.35% of total alkaloids calculated as hyoscyamine.

Geographical Source 

• A. belladonna is cultivated in United States, Canada, UK, Germany and India.

Cultivation and Collection 

• Plants are cultivated by sowing seeds in nurseries and seedlings are transplanted in April to moist, calcareous and loamy soil. Weeds are removed and manure is applied for proper growth of the crop. During flowering session leaves and flowering tops are cut at least three times in a year at an interval of two months from one to three years old plants. When the plant is four years old, roots are dug out. The collected drug is dried at 40–50°C. Un-dried leaves deteriorate and give off ammonia. Belladonna plant infected with the fungus Phytophthora belladonnae should be destroyed to prevent further infection. Sometimes the leaves are damaged by flea-bettle insect and the roots by a fungus.

Characteristics 

• The drug contains leaves, smaller stems of about 5 mm diameter, flowers and fruits. Leaves are stalked, brittle, thin, entire, long-pointed, 5–25 cm long, 2.5–12 cm wide, ovate lanceolate, slightly decurrent lamina, margine-entire, apex acuminate, colour dull-green or yellowish-green, surface glabrous, lateral veins join the midrib at an angle of 60°C, curving upwards and are anastomose. The upper side is darker than the lower. Each has a petiole about 0.5–4 cm long and a broadly ovate, slightly decurrent lamina about 5–25 cm long and 2.5–12 cm wide. The margin is entire and the apex acuminate. A few flow ers and fruits may be present. If the leaves are broken, they are characterized by the venation and roughness of the surface due to the presence of calcium oxalate in some mesophyll cells which causes minute points on the surface of the leaf on drying. The flowers blooming in June are solitary, shortly stalked, drooping and about 2.5 cm long. The corolla is campanulate, five-lobed and of a dull purplish colour. The five-lobed calyx is persistent, remaining attached to the purplish-black berry. The fruit is bilocular, contains numerous seeds and is about the size of a cherry. A yellow variety of the plant lacks the anthocyanin pigmentation.

Microscopy 

• A transverse section of the leaf of A. belladonna has a bifacial structure. The epidermal cells have-wavy walls and a striated cuticle. Anisocytic type and some of the anomocytic type stomata arc present on both surfaces but are most common on the lower. Hairs are most numerous on young leaves, uni-seriate, two- to four-celled clothing hairs; or with a uni-cellular glandular head. Some hair has a short: pedicel and a multicellular glandular head. Certain of the cells of the spongy mesophyll are filled with micro-sphenoidal (sandy) crystals of calcium oxalate. The midrib is convex above and shows the usual bicollateral vascular bundle. A zone of collenchyma is present in epidermis near midrib.

Chemical Constituents 

• Belladonna contains 0.3–1.0% total alkaloids, the prominent base is l-hyoscyamine and other components are atropine, apoatropine, as choline, belladonnine, cuscohygrine, chrysatropic acid, volatile bases, such as atroscine, leucatropic acid; phytosterol, N-methylpyrroline, homatropine, hyoscyamine N-oxide, rutin, kaempferol-3-rhamnogalactoside and 7-glucoside, quercetin-7-glucoside, scopoletin, calcium oxalate, 14% acid soluble ash and 4% acid-insoluble ash. Addition of ammonia to the alcoholic solution of scopoletin shows blue florescence. This test is useful to detect Belladonna poisoning. Atropine is formed by racemization during the extraction process

Uses 

• The drug is used as adjunctive therapy in the treatment of peptic ulcer; functional digestive disorders, including spastic, mucous and ulcerative colitis; diarrhoea, diverticulitis and pancreatitis. Due to anticholinergic property, it is used to control excess motor activity of the gastrointestinal tract and spasm of the urinary tract.

• Belladonna is anticholinergic, narcotic, sedative, diuretic mydriatic and used as anodyne and to check secretion. Otheruses are similar to Hyoscyamus. It relieves spasm of gut or respiratory tract. Consumption of Belladonna checks excessive perspiration of patients suffering from tuberculosis. Belladonna acts as a parasympathetic depressant. 

Marketed Products

• It is one of the ingredients of the preparation known as Belladona plaster (Surgi Pharma) for backache, stiffness of muscles and boil, swollen joints.

DATURA HERB

Biological Source

• Datura herb consists of the dried leaves and flowering tops of Datura metel Linn and Datura metel var. fastuosa belonging to family Solanaceae.

Geographical Source

• It is found in India, England and other tropical and subtropical countries

Characteristics

• Datura metel is also an Indian plant and resembles D. fastuosa; it differs in that the leaves are heart-shaped, almost entire and downy, and the flowers always white.

• D. metel var. fastuosa is known in commerce as black datura. The leaves are ovate and more or less angular, the flowers being mostly purplish, sometimes white. Corolla is double or triple. Outer corolla has five teeth and inner Corolla has six to ten teeth.

Microscopy

• Transverse section shows a bifacial structure. The following characters were observed in the lamina and the midrib region. In the lamina it has the upper epidermis which is single layer, rectangular cells covered with cuticle. Both covering and glandular trichomes are present. The covering trichomes are uni-seriate, multicellular, warty and with blunt apex. The glandular trichomes have one stalk consisting of one cell and multicellular head. The mesophyll has spongy parenchyma and palisade parenchyma in it. Palisade cells are radially elongated, single layer and compactly arranged. Spongy parenchyma are several layers, loosely arranged consisting of micro-sphenoidal crystals and vascular strands. In the midrib, strips of collenchyma appear below the upper and above the lower epidermis followed by the cortical parenchymatous cells containing calcium oxalate. The lower epidermis is similar to that of the upper one but has more number of trichomes and stomata when compared with upper epidermis.

Chemical Constituents

• Datura herb contains up to 0.5% of total alkaloids, among which hyoscine (scopolamine) is the main alkaloid, while l-hyoscyamine (scopoline) and atropine are present in very less quantities.

Chemical Tests

•  Vitali-Morin test: The tropane alkaloid is treated with fuming nitric acid, followed by evaporation to dryness and addition of methanolic potassium hydroxide solution to an acetone solution of nitrated residue. Violet colouration takes place due to tropane derivative. 

• On addition of silver nitrate solution to solution of hyoscine hydrobromide, yellowish white precipitate is formed, which is insoluble in nitric acid, but soluble in dilute ammonia

Uses

• In Ayurveda black datura is considered more efficacious or more toxic. D. metel is used in the manufacture of hyoscine or scopolamine. It exhibits parasympatholytic with anticholinergic and CNS depressant effects. The drug is used in cerebral excitement, asthma and in cough. The Rajpoot mothers are said to smear their breasts with the juice of the D. metel leaves, to poison their newly born female infants.

Other species

• D. arborea, a South American species (the Tree Datura), growing freely in Chile, contains about 0.44% alkaloid, nearly all hyoscines. A tincture of the flowers is used to induce clairvoyance. D. quercifolia, of Mexico, contains 0.4% in the leaves and 0.28% of alkaloids in the seeds, about half hyoscyamine and half hyoscine. Datura innexin is found throughout India. It is a perennial herb with a thick fleshy hairy stem. Leaves are thick and pubescent. Corolla is single, white, 10 toothed and calyx inflated. Fruit is a capsule with prominent spines. Leaves contain both hyoscine and hyoscyamine. Datura tatula, Purple Stramonium owes its activity to the same alkaloids as D. Stramonium, and its leaves are also much used in the form of cigarettes as a remedy for spasmodic asthma. D. ferox, Chinese Datura, is used in homoeopathy.

Marketed Products

• It is one of the ingredients of the preparations known as Jatifaladi Bati, Jatyadi tail (Baidyanath) and J.P. Massaj oil, Pain kills oil, J.P. Grace oil (Jamuna Pharma).

STRAMONIUM

Synonyms 

• Thorn apple leaves: Jimson or Jamestown weed; Dhatura; Stinkweed; Devil’s apple; Apple of Peru; Folia stramonii.

Biological Source 

• Stramonium consists of dried leaves and flowering tops of Datura stramonium Linn, or its variety D. tatula Linn., belonging to family Solanaceae. The drug is required to contain not less than 0.25% of alkaloids calculated as hyoscyamine. Prepared Stramonium is the finely powdered drug adjusted to an alkaloid content of 0.23–0.27%

Geographical Source 

• Stramonium is found widely in European, Asian, and American countries and in South Africa. The plant grows commonly in waste places throughout India from Kashmir to Malabar. It is cultivated in Germany, France, Hungary and South America

Cultivation and Collection 

• Datura prefers a rich calcareous soil. It can be grown from seeds in spring in drills; the plants are later thinned to stand 3 m apart in raws. The plant is sensitive to frost and sheltered situations are preferred for cultivation. Entire plants are cut down when the fruits are mature. Nitrogen manuring, which favours the growth of plants, also flavours alkaloid formation. At the end of August leaves and flowering tops are collected and dried at 45–50°C.

Characteristics 

• D. stramonium is a bushy annual herb, 1.5 m high, having whitish roots and numerous rootlets. The dried leaves are greyish green in colour, thin, brittle, twisted, broken, whole leaves 8–25 cm long and 7–15 cm wide; shortly petiolate, ovate or trian gular-ovate in shape, acuminate at the apex and have a sinuate-dentate margin. The margin possesses teeth dividing the sinuses; the lateral veins run into the marginal teeth.

Microscopy 

• A transverse section of a leaf has a bifacial structure; covered with a smooth cuticle and possess both stomata and hairs. Micro-sphenoidal and prismatic cluster crystals of calcium oxalate are abundant in the mesophyll. The stomata are of the anisocytic and anomocytic types. The epidermal cells have wavy walls. The uni-seriate clothing hairs are three- to five-celled, slightly curved and have thin, warty walls. Small glandular hairs with a one- or two-celled pedicel and anoval head of two to seven cells are also present. The midrib has a bicollateral structure and characteristic subepidermal masses of collenchyma on both surfaces. The xylem is a curved arc. Sclerenchyma is absent.

Chemical Constituents

• Stramonium contains 0.2–0.6% alkaloids. The main alkaloids are hyoscyamine and hyoscine (scopolamine). It also contains protein albumin and atropine.

• Atropine is formed from hyoscyamine by racemization. At the time of collection these alkaloids are usually present in the proportion of about two parts of hyoscyamine to one part of hyoscine, but in young plants hyoscine is the predominant alkaloid. The larger stems contain small amount of alkaloid, and the official drug should contain no more than 3% stem with a diameter exceeding 5 mm.

• Ditigloyl esters of 3,6-dihydroxytropane and 3, 6,7- trihydroxytropane have also been isolated from the roots in addition to hyoscine, hyoscyamine, tropine and pseudotropine,

• D. stramonium also contains 6-hydroxyhyoscyamine, skimmianine, meteloidine, acetyl derivatives of caffeic, p-coumaric and ferulic acids, β-sitosterol, stigmasterol, campesterol, with anolide I, steroidal glycosides daturataturins A and B; flavonoids chrysins, quercetin and kaempferol and their esters.

Uses

• It is a narcotic, antispasmodic and anodyne drug and used to relieve the spasm of the bronchioles in asthma. The leaves are ingredient of Pulvis stramonii compositus and other powders used for the relief of asthma. The leaves may be made into cigarettes or smoked in a pipe to relieve asthma. They are also used in the treatment of parkinsonism, boils, sores and fish bites. The flower juice is used to treat earache.

• The fruit juice is applied to the scalp for curing dandruff and falling hair. Stramonium ointment, containing lanolin, yellow wax and petroleum, is employed to cure haemorrhoids.

HYOSCYAMUS

Synonyms 

• Common Henbane, Hyoscyamus, Hog’s-bean, Jupiter’sbean, Symphonica, Cassilata, Cassilago, Deus Caballinus.

Biological Source 

• Hyoscyamus consists of the dried leaves and flowering tops of Hyoscyamus niger Linn., belonging to family Solanaceae. It contains not less than 0.05% alkaloids, calculated as hyoscyamine

CVGeographical

•  Source It is found throughout Central and Southern Europe and in Western Asia, extending to India and Siberia. As a weed of cultivation, it now grows also in North America and Brazil. Apart from these countries, it grows in Scotland, England and Wales and also in Ireland, and has been found wild in 60 British countries.

History 

• The medicinal uses of Henbane date from Ancients times, being particularly commended by Dioscorides (first century A.D.), who used it to procure sleep and allay pains, and Celsus (same period) and others made use of it for the same purpose, internally and externally. This use is mentioned in a work by Benedictus Crispus (A.D. 681) under the names of Hyoscyamus and Symphonica. There is frequent mention made of it in Anglo Saxon works on medicine of the eleventh century, in which it is named ‘Henbell’, and in the old glossaries of those days it also appears as Caniculata, Cassilago and Deus Caballinus.

• Later it was not used. It was omitted from the London Pharmacopoeia of 1746 and 1788, and only restored in 1809; its reintroduction being chiefly due to experiments and recommendations by Baron Storch, who gave it in the form of an extract, in cases of epilepsy and other nervous and convulsive diseases.

Cultivation and Collection 

• Drug is usually obtained from cultivated biennial herb. Henbane will grow on most soils, in sandy spots near the sea, on chalky slopes, and in cultivation flourishing in a good loam, It requires a light, moderately rich and well-drained soil for successful growth and an open, sunny situation, but does not want much attention beyond keeping the ground free from weeds. The seed should be sown in the open, early in May or as soon as the ground is warm, as thinly as possible, in rows 2–2.5 feet apart, the seedlings thinned out to 2 feet apart in the rows, as they do not stand transplanting well. In order to more readily ensure germination, it is advisable to soak the seeds in water for 24 h before planting the unfertile seeds will then float on the top of the water and may thus be distinguished. Ripe seed should be grey, and yellowish or brown seeds should be rejected, as they are immature. Let the seeds dry and then sift out the smallest, using only the larger seeds. Only the larger seedlings should be reserved, especially those of a bluish tint. The soil where the crop is to be, must have been well manured, and must be kept moist until the seeds have germinated, and also during May and June of the first year. It is also recommended to sow seeds of biennial Henbane at their natural ripening time, August, in porous soil. 

• The ground must never be water-logged, drought and late frosts stunt the growth and cause it to blossom too early, and if the climatic conditions are unsuitable, especially in a dry spring and summer, the biennial Henbane will flower in its’ first year, while the growth is quite low, but well manured soil may prevent this. Much of the efficacy of Henbane depends upon the time at which it is gathered. The leaves should be collected when the plant is in full flower. In the biennial plant, those of the second year are preferred to those of the first; the latter are less clammy and foetid, yield less extractive, and are medicinally considered less efficient. The leaves of the biennial variety are collected in June or the first week of July and those of the annual in August. They are dried at 40–50°C in drying sheds, heated from outside. The dried drug is stored in airtight containers at low temperature, protected from light and moisture.

Characteristics 

• Both varieties are used in medicine, but the biennial form is the one considered official. The leaves of this biennialplant spread out flat on all sides from the crown of the root like a rosette; they are oblong and egg-shaped, with acute points, stalked and more or less sharply toothed, often more than a foot in length, of a greyish-green colour and covered with sticky hairs. These leaves perish at the appearance of winter. The flowering stem pushes up from the root-crown in the following spring, ultimately reaching from 3 to 4 feet in height, and as it grows, becoming branched and furnished with alternate, oblong, unequally lobed, stalkless leaves, which are stem-clasping and vary considerably in size, but seldom exceed 9–10 inches in length. These leaves are pale green in colour, with a broad conspicuous midrib, and are furnished on both sides (but particularly on the veins of the under surface) with soft, glandular hairs, which secrete a resinous substance that causes the fresh leaves to feel unpleasantly clammy and sticky. Similar hairs occur on the sub-cylindrical branches.

• The flowers are shortly stalked, the lower ones growing in the fork of the branches, the upper ones stalkless, crowded together in one side, leafy spikes, which are rolled back at the top before flowering, the hairy, leafy, coarsely toothed bracts becoming smaller upwards. The flowers have a hairy, pitcher shaped calyx, which remains round the fruit and is strongly veined, with five stiff, broad, almost prickly lobes. The corollas are obliquely funnel-shaped, upwards of an inch across, of a dingy yellow or buff, marked with a close network of lurid purple veins. A variety sometimes occurs in which the corolla is not marked with these purple veins. The seed-capsule opens transversely by a convex lid and contains numerous small seeds.

Microscopy 

• The epidermis is covered with smooth layer of cuticle. Epidermis has slightly sinuous anticlinal walls and has covering and glandular trichomes along with anisocytic type of stomata. The covering trichomes are uni-seriate, multicellular with two- to four-celled, and the glandular trichomes have uni-seriate stalk with two to six cells and ovoid multicellular glandular head. The mesophyll is usually dorsiventral with single layer of palisade parenchymatous cells only below the upper epidermis and rarely isobilateral. A crystal layer is present below the palisade, with tetragonal prisms or clusters of few components. In the midrib region it has long narrow arc of radially arranged xylem above the phloem and an endodermis consisting of starch. The remaining portion is covered with parenchyma with small supernumerary phloem.

• The transverse section of stem shows a large central hollow and consists of numerous perimedullary phloem bundles in the pith region. Tetragonal calcium oxalate as prisms or clusters or in micro-sphenoidal sandy shape is also present in the pith.

Chemical Constituents

• The chief constituent of Henbane leaves is the alkaloid Hyoscyamine, together with smaller quantities of Atropine and Hyoscine, also known as Scopolamine, The proportion of alkaloid in the dried drug varies from 0.045% to 0.14%. Other constituents of Henbane are a glucosidal bitter principle called hyoscytricin, choline, mucilage, albumin, calcium oxalate and potassium nitrate. On incineration, the leaves yield about 12% of ash. The chief constituent of the seeds is about 0.5–0.6% of alkaloid, consisting of Hyoscyamine, with a small proportion of Hyoscine, The seeds also contain about 20% of fixed oil.

Uses 

• It is used as antispasmodic, hypnotic and mild diuretic. The leaves have long been employed as a narcotic medicine. It is similar in action to belladonna and stramonium, thoughmilder in its effects. The drug combines the therapeutic actions of its two alkaloids, hyoscyamine and hyoscine. Because of the presence of the former, it tends to check secretion and to relax spasms of the involuntary muscles, while through the narcotic effects of its hyoscine it lessens pain and exercises a slight somnifacient action. It will also relieve pain in cystitis. It is used to relieve the griping caused by drastic purgatives, and is a common ingredient of aperient pills, especially those containing aloes and colocynth.

Marketed Products 

• It is one of the ingredients of the preparations known as Muscle and joint rub (Himalaya Drug Company), Brahmi vati, Sarpagandhaghan Vati (Dabur) and Zymnet drops (Aimil Pharmaceuticals).

COCA LEAVES

Biological Source 

• Coca consists of the dried leaves of various species of Erythmxylon, that is, Erythroxylon coca Lam (Huanco or Bolivian coca) or Erythroxylon coca var. Spruceanum (Peruvian, Truxillo or Java coca) also known as Erythroxylon truxillense Rusby., belonging to family Erythroxylaceae

Geographical 

• Source It is mainly found in Bolivia, Peru, Indonesia, Ceylon, Java and India.

Cultivation 

• Coca shrubs grow well in the situations similar to tea plantations. It requires rich, light and well-drained soil at an altitude of 1,500–6,000 m. Cultivation is carried out by sowing seeds. Fertilizers have their effects over these plants. In the second year the leaves will be matured enough to collect in dry weather. The collected leaves are dried in shade and packed.

Characteristics 

• Erythroxylon coca: leaves are brownish green in colour, oval, entire and glabrous, with a bitter taste, 3–8 cm long and 1.5–4 cm wide. Erythroxylon truxillense: the leaves are much smaller and pale green in colour, elliptical, entire, glaborous, not glossy, with bitter taste.

Microscopy 

•  The epidermis has straight anticlinal walls and stomata present are of the rubiaceous type only on the lower surface. The mesophyll reveals the presence of single layer of palisade parenchyma cells only below the upper epidermis. Prism of calcium oxalate crystals are seen in the spongy parenchyma. The midrib has vascular bundle composed of xylem and phloem with a band of pericyclic fibres below and few sclerenchyma above. Leaf has an outstanding ridge, filled with collenchyma, presence of lignified idioblasts, and development of sclerenchyma above and below the side veins are its unique characters.

Chemical 

• Constituents Coca leaves contain the alkaloids Cocaine, Annamyl Cocaine, and Truxilline or Cocamine. Truxillo or Peruvian leaves contain more alkaloid than the Bolivian, though the latter are preferred for medicinal purposes. Java Coca contains tropacocaine and four yellow crystalline glucosides in addition to the other constituents.

Uses 

• The actions of Coca depend principally on the alkaloid Cocaine. Cocaine has stimulant action on CNS. The leaves are extensively chewed to relieve hunger and fatigue. Coca alkaloids cause also hallucination. Coca leaves are

• used as a cerebral and muscle stimulant, especially during convalescence, to relieve nausea, vomiting and pains of the stomach without upsetting the digestion. Cocaine also has local anesthetic action on skin and mucous membrane; and is used as dental anaesthesia and minor local surgery of ophthalmic, ear, nose and throat. Chemical structure of cocaine has lead to several synthetic annaesthetics like anaesthesia, novocain, stovain, etc

DUBOISIA

Characteristics 

• Duboisia hopwoodii: Perennial shrub to 3 m, sometimes as small tree with brown to purplish bark on the young stems and corky older bark. Leaves are narrow, long and alternate to 15 cm, with recurved point and straight margins. Open clusters of white (with purple striped tube) flowers at the end of the branches. Black berry to 6 mm, containing one to two seeds in a dark pulp.