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ALKALOIDS INTRODUCTION, The term alkaloid was introduced by W. Meissener ., The definition of alkaloids is not simple and precise and sometimes it is, difficult to distinguish the thin line between alkaloids and other natural, nitrogen containing metabolites., Natural nitrogen containing compound are:,  Amino acids,  Amines,  Alkaloids,  Indole,  Purines, pyrimidines and cytokinins,  Cyanogenetic glycosides,  Chlorophylls, Definition: alkaloid is an organic compound of natural origin which, contains nitrogen atom., Pseudo alkaloids most often have all of the characteristics of the true, alkaloid but they are not derived from amino acids. Some of the most, known examples are Isoprenoid, Aconite, Aconine, Hypoaconitine etc., Proto alkaloids are simple amines in which the nitrogen atom is not part, of heterocyclic ring. They are basic in nature and derived from amino, acids. Few examples of these are Colchicine, Ephedrine and Pseudo, ephedrine., Alkaloids occur exceptionally in bacteria (Pseudomonas aeruginosa) and, rather rarely in fungi (Psilocin from the hallucinogenic mushroom)., In the plant, alkaloid occurs as soluble salt (citrate, Malate, tartarate,, melonates,benzoates, isobutyrates) or in combination with tannins., They are often localized in peripheral tissue external layer of the bark, and root or seed tegument. Alkaloids synthesis takes place at specific, sites (growing root, chloroplast, laticiferous cell).

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FUNCTIONS OF ALKALOIDS, 1. They are reserve substances which can supply nitrogen., 2. They are defensive mechanism for plant growth in dry region to, protect from grazing animals, herbivores and insects., 3. They are the end product of detoxification mechanism in plant and by, this way check formation of substance which may be prove to harmful to, the plant., 4. The possible role as growth regulatory factor in the plant., 5. They are present normally in conjugation with plant acid like, mercuric acid, cinchotannic acid etc. Therefore alkaloids could be acting, as carriers within plant for transportation of such acids., PHYSICOCHEMICAL PROPERTIES, • Alkaloids have molecular weight from 100-900., • Although most of the bases that do not contain oxygen atom are liquid, at ordinary temperature (examples: nicotine, coniine)., Those that do contain oxygen atom are normally crystallisable solids, and in rare cases they are coloured compound (example berberine)., • Almost all of the crystallized bases rotate the plane of polarized light, and have melting points without decomposition especially below 200⁰C., • As a general rule alkaloids as bases are not soluble in water. They are, soluble in polar or slightly polar organic solvents., • The basicity of alkaloids varies greatly. Since this property depends, entirely on the availability of the lone pair of electron on the nitrogen, atom., • Electron withdrawing group in close proximity to the nitrogen atom, decrease the basicity, whereas electron donating group enhances it.

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• The basic character allows the formation of salts with mineral acids, (i.e. hydrochloride, sulphates, and nitrates) and organic acids (i.e., tartarate, sulfonate)., • Alkaloidal salts are generally soluble in water and in dilute alcohols, and they are except in rare cases not soluble in organic solvent., • Pseudo alkaloids and proto alkaloids show higher solubility in water, while free bases of alkaloids are soluble in organic non polar immiscible, solvent., DETECTION, • Mayer reagent (Potassium mercuric iodide solution) gives cream, coloured precipitate., • Dragendorff reagent (Potassium bismuth iodide solution) shows, reddish brown precipitate., • Wagner reagent (Iodine potassium Iodide solution) yields reddish, brown precipitate., • Hagers reagent (saturated Picric acid solution) gives yellow colour, precipitate., CLASSIFICATION., Pharmacological Classification, Depending on the physiological response the alkaloids are classified, under various pharmacological categories like CNS stimulants or, depressant, sympathomimetics, analgesics, purgatives etc., Main drawback of this system is that it does not take into consideration, about chemical nature of crude drug. Within the same drug the, individual, alkaloids may exhibit different action., Example1) Morphine is narcotic and analgesic while codeine is mainly, antitussive.

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2) Cinchona quinine is antimalarial whereas quinidine is cardiac, depressant., 2. Taxonomic Classification, This method classifies the vast number of alkaloids based on their, distribution in various plant families like solanaceous alkaloids in, solanaceae family or papillionaceous alkaloids in papillionaceae family., The grouping of alkaloids are done as per the name of genus in which, they occur e.g. Ephedra, cinchona etc. The chemotaxonomic, classification has been further derived from this classification., 3. Biosynthetic Classification, This method gives the significance to the precursor from which the, alkaloids are biosynthesized in the plant. Hence the variety of alkaloid, with different taxonomic distribution and physiological activities can be, brought under some group if they are, derived from same precursor i.e. all indole alkaloid from tryptophan are, grouped together., Alkaloidal drugs are categorised on the fact whether they are derived, from amino acids precursor as ornithine, lysine, phenylalanine,, tryptophan etc., , 4. Chemical Classification, This is the most accepted way of classification of alkaloids which, basically depends on ring structure present in the alkaloid. The, alkaloidal drugs are broadly categorized into two divisions:, • True alkaloids (subdivided into 12 groups).

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RAUWOLFIA, Synonyms -Sarpagandha, Chandrika; Chootachand; Indian snake root., Biological Source, Rauwolfia consists of dried roots of Rauwolfia serpentina Benth., belonging to, family Apocynaceae., Geographical Source- It is an erect, evergreen, small shrub native to the Orient, and occurs from India to Sumatra. It is also found in Burma, Thailand, Philippines,, Vietnam, Indonesia, Malaysia, Paki-stan and Java. In India it occurs in the subHimalayan tracts from Sirhind eastwards to Assam, especially in Dehradun,, Siwalik range, Rohelkhand, Gorakhpur ascending to 1,300 m, east and west ghats, of Tamil Nadu, in Bihar (Patna and Bhagalpur), Konkan, Karnataka and Bengal., Cultivation and Collection - Rauwolfia grows in tropical forests at an altitude of, 1,200– 1,300 m at temperature 10–40°C. There should be enough rain or irrigation, for its cultivation. The soil should be acidic (pH 4–6), clayey and manure is, applied for better crop. Propagation is done by planting seeds, root cuttings or stem, cuttings. Better drug is obtained when the propaga-tion is carried out with fresh, seeds. The plants should be protected from nematodes, fungus and Mosaic virus., The drug is collected mainly from wild plants. Roots and rhizomes are dug out in, October–November when the plant roots are two to four years old. The aerial parts, and roots are separated. The roots are washed and dried in air. The roots containing, moisture up to 12% should be protected from light. Seasonal variation, genetic, differences, geographic location, improper handling and drying, and other factors, account for percentage differences in alkaloid amount. Rauwolfia should be

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packaged and stored in well-closed containers in a cool, dry place that is secure, against insect attack., Characteristics, The roots and rhizomes are almost identical in external characters. The drug occurs, in cylindrical or slightly tapering, tortuous pieces, 2–10 cm long, 5–22 mm in, diameter. The roots are rarely branched. Rootlets, 0.5–1 mm in diameter, are rare., The outer surface is greyish-yellow, light-brown or brown. Young pieces contain, slight wrinkles while old pieces have longitudinal ridges. Circular scars of root-lets, Microscopy, Transverse section of the root shows a stratified cork, which is divided, into two to, eight alternating zones. It consists of one to seven layers of smaller and radially, narrower, suberised, nonlignified cells alternating with one to three layers of larger, radially broader, lignified cells. The phelloderm is composed of about ten to twelve, layers of tangentially elongated to isodiametric, cellulosic parenchymatous cells., Cells of secondary cortex are parenchymatous and contain starch grains, simple, and compound (two to four components), spherical with a distinct hilum in the, form of a split. Phloem is narrow and consists of parenchyma with scattered sieve, tissue; parenchyma alternate with broader medullary rays composed of large cells, and usually two to four cells wide. Xylem is wide, entirely lignified and usually, shows two to five annual rings. Medullary rays, one to five cells wide, contain, starch grains and alternate with secondary xylem consisting of vessels, tracheids,, fibres and parenchyma. Xylem vessels have pitted thickening.

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serpentine, serpentinine, tetrahydroreserpine, raubasine, reserpinine, isoajamaline, and yohambinine., , The other substances present are phytosterols, fatty acids, unsaturated alcohols and, sugars., Uses, Rauwolfia in used as hypnotic, sedative and antihypertensive. It is specific for, insanity, reduces blood pressure and cures pain due to affections of the bowels. It, is given in labours to increase uterine contractions and in certain neuropsychiatric

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disorders. Ajmaline, which has pharmacological properties similar to those of, quinidine, is marketed in Japan for the treatment of cardiac arrhythmias., Reserpine is a white or pale buff to slightly yellow, odourless, crystalline powder, that darkens slowly when exposed to light and rapidly when in solution. Reserpine, is an antihypertensive and tranquilizer. Rescinnamine is the methyl reserpate ester, of 3,4,5-trimethoxy cinnamic acid. The usual antihypertensive dose of, rescinnamine is 500 μg, two times a day. Higher doses may cause serious mental, depression. Deserpidine is 11-des-methoxyreserpine. It is a wide-range tranquilizer, and antihypertensive and is free from the side effects., Marketed Products, It is one of the ingredients of the preparations known as Confido, Lukol, Serpina, (Himalaya Drug Company) and Sarpagandhan bati (Baidyanath), 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 belladonna is cultivated in United States, Canada, UK,, Germany and India.

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Cultivation and Collection, Plants are cultivated by sowing seeds in nurseries and seed-lings 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 deterio-rate 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 flowers 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

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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 fourcelled clothing hairs; or with a uni-cellular glandular head. Some hair has a short:

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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, chrysa-tropic acid, volatile bases, such as atroscine, leucatropic acid;, phytosterol, N-methylpyrroline, homatropine, hyoscyamine N-oxide, rutin,, kaempferol-3-rhamnogalactoside, , and, , 7-glu-coside,, , 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. Other uses 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.

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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., OPIUM, Synonyms- Crude Opium; Raw Opium; Gum Opium; Afim., Biological Source, Opium is the air dried milky latex obtained by incision from the unripe capsules of, Papaver somniferum Linn, or its variety P. album Decand., belonging to family, Papaveraceae., Opium is required to contain not less than 10% of morphine and not less than 2.0%, of codeine. The thebaine content is limited to 3%., Geographical Source, It is mainly found in Turkey, Russia, Yugoslavia, Tasmania, India, Pakistan, Iran,, Afghanistan, China, Burma, Thailand and Laos. In India, Opium is cultivated in, M.P. (Neemuch) and U.P. for alkaloidal extraction and seed production., History, The cultivation of opium dates back to 3400 B.C. in Mesopotamia and by 1300, B.C. Egyptians began the cultivation of opium thebaicum. Hippocrates ‘the father, of medicine’, (460–357 B.C.) prescribed drinking the juice of the white poppy

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mixed with the seed of nettle and also acknowledged its use as narcotic and styptic, in internal diseases. It was Alexander the Great, who introduced opium to India, and Persia. During the 17th century tobacco smoking was introduced in China,, which resulted in its extensive. In 1800 control on opium supply and prices was, brought and in 1805 Friedrich W. Seiturner (German pharmacist) isolated and, identified the chief chemical constituent of opium. The compound isolated was, named morphium (morphine) after Morpheus, the god of dreams. Eventually many, other constituents like codeine (1832) and papaverine (1848) were also isolated, and identified. Due to the uncontrolled use of opium in china (late 18th century), the imperial court had to ban its use. The United States in 19th century made easy, availability of the opium preparations and the ‘patent medicines’. Later on during, the war, the Union Army were provided with enough amount of opium pills,, laudanum, morphine sulphate, etc., which made opium addiction known as the, ‘army disease or the ‘soldier’s disease’., By 1870s, substitute for morphine by acetylating morphine were prepared and in, 1898 a German company manufactured 3, 6-diacetylmorphine (Heroin) in bulk, quantity. In December 1914, Harrison Narcotics Act which called for control of, each phase of the preparation and distribution of medicinal opium, morphine,, heroin, cocaine, and any new derivative with similar properties, was enforced by, the United States Congress. The Federal Controlled Substances Act of 1970 is the, redefined act of the Har-rison Act. In 1999, opium was declared as the Bumper, crop of Afghanistan by producing 75% of world’s heroin. In December 2002 the, U.K. government under the health plan, will make heroin available free on, National Health Service to all those with a clinical need for it.

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Cultivation and Collection, Opium is cultivated under license from the government. Its seeds are sown in, October or March in alluvial soil. After germination of seeds snow falls. In spring, the thin plant attains the height of 15 cm. Fertilizers are used for better crop. The, poppy of first crop blossoms in April or May and the capsule mature in June or, July. When the capsules are about 4 cm in diameter, the colour changes from green, to yellow; they are incised with a knife about 1 mm deep around the circumference, between midday and evening. The knife, known as a ‘nushtur’ bears narrow iron, spikes which are drawn down the capsule to produce several longitudinal cuts. The, incision must not penetrate into the interior of the capsule otherwise latex will be, lost. The latex tube opens into one another. The latex, which is white in the, beginning, immediately coagulates and turns brown. Next morning it is removed, by scrapping with a knife and transferred to a poppy leaf. Each capsule is cut, several times at intervals of two or three days. After collection the latex is placed, in a tilted vessel so that the dark fluid which is not required may drain off. By, exposure to air the opium acquires a suitable consistency for packing. The dried, latex is kneaded into balls, wrapped in poppy leaves and dried in shade. The, principal commercial varieties of Opium are Turkish Opium, Indian Opium,, Chinese Opium, Yugoslavian Opium and Persian Opium., Characteristics, Opium occurs in rounded or flattened mass which is 8–15 cm in diameter and, weighing from 300 g to 2 kg each. The external surface is pale or chocolate-brown,, texture is uniform and slightly granular. It is plastic like when fresh and turns hard, and brittle after sometime. Fragment of poppy leaves are present on the upper, surface. Internal surface is coarsely granular, reddish-brown, lustrous; odour is

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characteristic; taste is bitter and distinct. Opium is intended only as a starting, material for the manufacture of galenical preparations and is not dispensed as such., , Papaver somniferum capsules, Chemical Constituents, Opium contains about 35 alkaloids among which morphine (10–16%) is the most, important base. The alkaloids are combined with meconic acid. The other alkaloids, isolated from the drug are codeine (0.8–2.5%), narcotine, the-baine (0.5–2%)., noscapine (4–8%), narceine and papaverine (0.5–2.5%). Morphine contains a, phenanthrene nucleus. The different types of alkaloids isolated are:

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hydroxycinchonic acid, phthalic acid, hemipinic acid, meconin and an, odorous compound have also been reported., , Chemical Tests, Aqueous extract of Opium with FeCl3 solution gives deep reddish purple colour, which persists on addition of HCl. It indicates the presence of meconic, acid.Morphine gives dark violet colour with conc. H2SO4 and formaldehyde., Uses, Opium and morphine have narcotic, analgesic and sedative action and used to, relieve pain, diarrhoea dysentery and cough. Poppy capsules are astringent,, somniferous, soporific, sedative and narcotic and used as anodyne and emollient., Codeine is mild sedative and is employed in cough mixtures. Noscapine is not, narcotic and has cough suppressant action acting as a central antitussive drug.

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Papaverine has smooth muscle relaxant action and is used to cure muscle spasms., Opium, morphine and the diacetyl derivative heroin, cause drug addiction.