Alkaloid
Introduction
• The term alkaloids (or alkali-like) was first and foremost proposed by the pharmacist, W. Meissner, in 1819, for the basic nitrogen-containing compounds of plant origin.
• Some characteristic features of alkaloid :
(a) Complex molecular structure, and
(b) Significant pharmacological activity.
Nomenklature • The major characteristic of the nomenclature of alkaloids is the lack of any agreed
systematic prevailing system. Therefore, by a general agreement, the chemical rules designate that the names of all alkaloids must end with the suffix (–ine). The latin names end with (–ina).
• Thus, the names of the alkaloids are usually obtained in a number of ways, namely: (a) From the generic name of the plant producing them: Examples: Atropine from Atropa belladona Linn., (Solanaceae); and Hydrastine from
Hydrastis canadenisis L. (Ranunculaceae). (b) From the specific name of the plant yielding them: Examples: Belladonine from Atropa belladona L. (Solanaceae); and Cocaine
from Erythroxylum coca Lam. (Erythroxylaceae). (c) From the common name of the drug producing them: Example: Ergotamine from Claviceps purpurea (Er.) Tul. (Hypocreales) commonly known as
ergot. (d) From their specific physiological activity: Examples: Emetine from Hedera helix L. (Araliaceae) called Ivy; Narcotine from Papaver
somniferum L. (Papaveraceae) known as Opium Poppy; and Morphine from P. somniferum L. (e) From the name of the discoverer: Example: Pelletierine from the barks of Puniea granatum Linn., (Punicaceae). (f ) From their physical property: Example: Hygrine from the roots of Withania somniferum (L.) Dunal (Solanaceae) called
Ashwagandha (Hygro = moist).
Distribution
• McKee* (1962) reported that about 1000 alkaloids, which are known, belong to almost 100 families, 500 genera and spread over 1200 species. However, it has been observed beyond reasonable doubt that the alkaloids are not evenly distributed amongst the plant kingdom. They have been found to be absent in Algae and in the lower groups of plants with the exception of one or two families of the fungi. The glaring examples of fungal alkaloids include those of ergot alkaloids.
• However, in the plant kingdom, the alkaloids generally, seem to get confined to a certain families and genera with regard to their distribution. For instance, amongst the angiosperms the families which have been recognized as outstanding for alkaloidal-yielding plants are, namely: Apocynaceae, Berberidaceae, Papaveraceae, Ranunculaceae, Rubiaceae and Solanaceae.
• Monocotyledons, generally do not produce alkaloids, but investigation have revealed that two of the most promising families viz., Amaryllidaceae and Liliaceae do contain alkaloid-containing plants.
• Dicotyledons, mostly contain the alkaloids. It has been observed that neither Labiatae nor Rosaceae contain any alkaloid. Furthermore, almost 15% of all vascular plants contain alkaloids.
Occurrence
• Alkaloids may occur in various parts of the plant. It may, however, be pointed out that in a particular species, normally only one or two specific organs and not all organs, essentially afford the function of alkaloidal formation.
• For instance, the alkaloids of the tobacco plant, Nicotiana tabacum Linn., (Solanaceae), are produced in the root and are subsequently translocated to the leaves where they usually accumulate, whereas the seeds are completely devoid of alkaloid.
• In another glaring example the opium poppy, Papaver somniferum, the alkaloids solely occur in the fresh latex of the fruit, while the seeds of poppy are virtually devoid of alkaloids.
• Likewise, the colchicum** corm. Colchicum autumnale Linn. (Liliaceae), the alkaloids are found both in the seed and in the corm.
• Interestingly, the bark of cinchona tree, Cinchona officinalis Linn., (Rubiaceae) contain the alkaloids (viz., quinine) exclusively.
• Salts of Alkaloids It has been found that a plethora of alkaloids occurring in various plant species are in the form of salts of organic acids, such as: acetic acid, malic acid, oxalic acid, succinic acid, tartaric acid, tannic acid or some other specific plant acids. In certain instances, the alkaloids are found to be in combination with special plant acids
Function of Alkaloids in Plants
(a) As strategically located poisonous agents in plants thereby protecting them either against herbivorous animals or insects,
(b) As probable by-products of various detoxification reactions representing a metabolic lockingup of compounds, otherwise harmful or detrimental to the plant,
(c) As pronounced regulatory growth factors, and (d) As reserve substances in plant capable of
supplying nitrogen or other necessary elements to its economy.
Isomerism
• A plethora of alkaloids contain one or more asymmetric carbon atoms in the molecule, and hence exhibit optical activity. It has been observed that in the majority of instances only the (–)- isomer (i.e., the levorotatory component) has appreciable and distinct pharmacological activity than the corresponding (+)-isomer (i.e., the dextrorotatory, component) of the same alkaloidal species.
• In fact, the optical activity is invariably associated with the alkaloids and their respective salts. However, the optical activity and the specific rotation usually varies with the solvent used, the temperature, the wave length of light and other minor factors.
Relative pressor activities* of D(–)-ephedrine and D(+) ephedrine: The relative pressor activities of D(–)-ephedrine is found to be 36 with regard to its D(+)-ephedrine isomer at ll i.e., the former is almost 3½ times more active than the latter
Antimigraine activity of (–)-ergotamine and (+)-ergotamine: It has been observed that the antimigraine activity of (–)-ergotamine possesses 3-4 times more activity than its corresponding (+)-ergotamine isomer
Showing both (–)-and (+)-forms active pharmacologically: In certain alkaloids, the (–) form as well as the (+) form are medicinally useful. Examples: The (–)-Quinine is primarily employed as a potent antimalarial agent; whereas the (+)-Quinine, also known as quinidine, is solely used in restoring cardiac arrythmia to normal rythm
General Characteristics of Alkaloids
• The general characteristics of alkaloids may be grouped together in two categories, namely:
(a) Physical characteristics, and
(b) Chemical characteristics.
Physical Characteristics : Solubitily
• However, it has been observed that the free alkaloid bases as such are invariably found to be fairly soluble in organic solvents, such as: either, chloroform, relatively non-polar solvents (hexane, benzene, petroleum ether), immiscible solvent, lower alcohols (methanol, ethanol); but they are either practically insoluble or very sparingly soluble in water.
• Interestingly, the alkaloidal salts are almost freely soluble in water, relatively less soluble in alcohol and mostly either insoluble or sparingly soluble in organic solvents
• Examples Atropine sulphate and morphine hydrochloride are much more soluble in water than their corresponding bases i.e., atropine and morphine
Physical Characteristics : Solubitily
• However, there are a few exceptions to the above stated generalizations, namely:
(i) Certain alkaloid bases are water soluble, but these may be solely regarded as exceptions rather than any specific rule, such as: ephedrine, colchicine, pilocarpine; the quaternary alkaloid-base like berberine and tubocurarine; caffeine-base readily extracted from tea with water.
(ii) Narceine and pilocarpine are insoluble in organic solvents, whereas morphine is sparingly soluble in organic solvents viz., solubility in either 1:5000.
(iii) Certain alkaloidal salts, for instance: lobeline hydrochloride and apoatropine hydrochloride are found to be soluble in organic solvent like chloroform.
(iv) Some alkaloidal salts are sparingly soluble in water whereas others are extremely watersoluble, such as: Quinine sulphate-soluble in 1:1000 parts of water, Quinine hydrochloride soluble in 1:1 part of water.
Chemical Characteristics : basicity
Chemical Characteristics : Salient Features
1. The weaker bases, i.e., alkaloids having low pKa values, shall require a more acidic medium to form their respective salts with the corresponding acid.
2. The strongly basic alkaloids i.e., those possessing high pKa values, shall require comparatively low acidic medium to form their respective salts with the acid.
3. The alkaloids are usually neutrallized with acids to form salts that may be converted to the corresponding free-base by the cautious addition of selective weak bases, such as, ammonia, calcium hydroxide or sodium carbonate. The usage of either NaOH or KOH solutions must be avoided so as to prevent the decomposition or destruction of highly sensitive alkaloids.
4. Amphoteric alkaloids: There are some alkaloids which are amphoteric in nature i.e., they are neither acidic nor basic in character; this is due to the presence of phenolic (–OH) moiety in Morphine, or the presence of carboxylic (–COOH) function in Narceine
5. Unstable alkaloidal salts: There exists some specific alkaloids that inherently possess weakbasic properties and their salts are not so stable, for instance: piperine, papaverine, narceine, narcotine, and caffeine.
6. Neutral or slightly acidic alkaloids: There are a few typical naturally occurring alkaloids that almost behave as either neutral or slightly acidic character, namely: ricinine and theophylline
Chemical Characteristics : Stability
Alkaloids, in general, are not very stable. They normally undergo degradation or decomposition on being exposed to air, light, moisture and heat, besides chemical reagents. A few typical examples of alkaloids vis-a-vis their stability are stated below, namely: (i) Ergotamine gets destroyed by prolonged treatment with alkali, whereas
strychnine can stand such vigorous action. (ii) An aqueous solution of alkaloids undergo rapid decomposition or degradation
as compared to their solid forms. (iii) Storage of alkaloids in pure form or their dry extracts is usually done in a
vacuum desiccator over a dehydrating agent e.g., phosphorous pentoxide (P2O5) or calcium chloride (CaCl2) anhydrous for their better stability.
(iv) During the course of extraction of alkaloids followed by isolation, the solvent is preferably removed effectively by distillation under vacuum** (or reduced atmospheric pressure) or by subjecting it to evaporation in a Rotary Thin-Film Evaporator under vacuum so that the desired product is not exposed to excessive heat, thus avoiding decomposition.
(v) Alkaloids, are stored in amber-coloured glass bottles preferably in a vacuum desiccator.
CLASSIFICATION OF ALKALOIDS
• the alkaloids have been divided into two major categories based on the analogy that one containing a non-heterocyclic nucleus, while the other having the heterocyclic nucleus.
(a) Non-heterocyclic Alkaloids
(b) Heterocyclic Alkaloids
CLASSIFICATION OF ALKALOIDS
A. Alkaloids derived from Amination Reactions
(i) Acetate-derived Alkaloids (ii) Phenylalanine-derived Alkaloids (iii) Terpenoid Alkaloids (iv) Steroidal Alkaloids B. Alkaloids derived from Anthranilic Acid (i) Quinazoline Alkaloids (ii) Quinoline Alkaloids (iii) Acridine Alkaloids C. Alkaloids derived from Histidine Imidazole Alkaloids D. Alkaloids derived from Lysine (i) Piperidine Alkaloids (ii) Quinolizidine Alkaloids (iii) Indolizidine Alkaloids E. Alkaloids derived from Nicotinic Acid Pyridine Alkaloids
F. Alkaloids derived from Ornithine (i) Pyrrolidine Alkaloids (ii) Tropane Alkaloids (iii) Pyrrolizidine Alkaloids G. Alkaloids derived from Tyrosine (i) Phenylethylamine Alkaloids (ii) Simple Tetrahydro iso-quinoline Alkaloids (iii) Modified Benzyl Tetrahydro iso-quinoline
Alkaloids H. Alkaloids derived from Tryptophan (i) Simple Indole Alkaloids (ii) Simple b-Carboline Alkaloids (iii) Terpenoid Indole Alkaloids (iv) Quinoline Alkaloids (v) Pyrroloindole Alkaloids (vi) Ergot Alkaloids
Alkaloids Derived from Amination Reactions
• An extensive and intensive studies on certain alkaloids it has been observed that the N-atom is specifically donated from an amino acid source through a transamination reaction using an appropriate ketone or aldehyde
A. Alkaloids derived from Amination Reactions
(i) Acetate-derived Alkaloids
(ii) Phenylalanine-derived Alkaloids
(iii) Terpenoid Alkaloids
(iv) Steroidal Alkaloids
(i) Acetate-Derived Alkaloids
• Biological Sources It is obtained from the unripe, fully grown dried fruits of Conium maculatum L. (Umbelliferae). It also occurs in the plant Aethusa cynapium L. (Apiaceae) (Fool’s Parsley); Cicuta maculata L.(Apiaceae) (Water Hemlock).
• Uses Externally, the coniine salts are used as ointments and infrequently employed for their local analgesic action in the symptomatic relief of pruritis, hemorrhoids and fissures.
• Caution It exhibits potential symptoms of over exposure as: weakness, drowsiness, parasthesias, ataxia, nausea, excessive salivation, and bradycardia followed by tachycardia.*
(ii) Phenylalanine-Derived Alkaloids
• Biological Source It occurs in the dried young stems of the Chinese wonder drug Ma Huang, Emhedra vulgaris, Ephedra sinica Stapf., Ephedra equisetina Bunge belonging to family Ginetaceae. This is also found in Ephedra geradiana Wall ex. Stapf. (Ephedraceae) (Pakistani Ephedra). There are two most important forage ephedras in the United States, namely: E. nevadensis and E. viridis. The former are is E. nevadensis S. Wats (Ephedraceae) and known as Mormon Tea and Nevada Jointfir.
• Uses l. l-Ehedrine is used extensively as a bronchodilator. 2. It also exerts excitatory action on the CNS and produces
noticeable effects on skeletal muscles. 3. It is also employed as nasal decongestant.
• Biological Source It is the pungent principle obtained in the fruit of various species of Capsicum, viz., Capsicum annum L. (Solanaceae) (Chilli, Sweet Peppers, Paprika)
• Uses 1. It is used as a topical analgesic. 2. It is often employed as a tool in neurobiological
research. 3. It is used in creams to counter neuralgia caused
by herpes infections and in other pain-relieving formulations.
(ii) Phenylalanine-Derived Alkaloids
(iii) Terpenoid Alkaloids
• Biological Source Aconine is the hydrolyzed product of aconitine which is obtained from the dried roots of Aconitum napellus Linn. (Ranunculaceae) and other aconites. A. napellus in also known as aconite, blue rocket and monkshood
• Uses
1. It is used in the treatment of neuralgia, sciatica, rheumatism and inflammation.
2. It is employed occasionally as analgesic and cardiac depressant.
(iii) Terpenoid Alkaloids
• Biological Source The botanical source is the same as aconine
• Uses
1. It is exclusively used in producing heart arrythmia in experimental animals.
2. It has also been used topically in neuralgia.
(iv) Steroidal Alkaloids
• The steroidal alkaloids may be broadly classified into two major groups, namely:
(a) Solanum Alkaloids, and
(b) Veratrum Alkaloids.
(iv a) Solanum Alkaloids
• Biological Sources It is obtained from the fruits of Capsicum annuum L. (Solanaceae) (Chili, Paprika, Sweet Peppers); shoots and berries of S. dulcamara L. (Solanaceae) (Bittersweet, Bitter Nightshade, Felonwood); leaves of S. nigrum L. (Solanaceae) (Wonderberry, Black Nightshade,Prairie Huckleberry).
• Uses It is invariably used as a starting material for steroidal drugs.
(iv b) Veratrum Alkaloids
• Biological Sources It is obtained from the rhizome of Veratrum album L. (Liliaceae) and Veratrum viride Ait. (Liliaceae) (American Hellebore).
• Uses 1. It is used as an antihypertensive agent which exerts its
action through reflex inhibition of pressor receptors in the heart and carotid sinus.
2. It also possesses emetic action. 3. It is used in the treatment of toxemia of pregnancy.
Alkaloids Derived from Anthranilic Acid
• The alkaloids derived from anthranilic acid may be classified into three major categories, namely:
(i) Quinazoline alkaloids,
(ii) Quinoline alkaloids, and
(iii) Acridine alkaloids
(i) Quinazoline Alkaloids
• Biological Sources It is obtained from the leaves of Adhatoda vasica (L.) Nees (Acanthaceae) (Malabar Nut, Adotodai, Paveltia); and the seeds of Peganum harmala L. (Rutaceae) (Harmel, Syrian Rue, African Rue)
• Uses 1. It is mostly used as an expectorant and bronchodilator. 2. It also shows oxytocic properties very similar to those
exhibited by oxytocin and methyl ergometrine. 3. Vasicine also shows abortifacient action which is due to the
release of prostaglandins.
(i) Quinazoline Alkaloids
• Biological Source The plant source remain the same as described under vasicine
• Uses It is used mainly as an expectorant which action is solely due to stimulation of the bronchial glands.
(ii) Quinoline Alkaloids
• Biological Sources It is obtained from the bark of Cinchona calisaya Wedd; Cinchona ledgeriana Moens ex Trimen; Cinchona officinalis Linn. f.; Cinchona robusta How; and Cinchona succirubra Pavon ex Klotzsch belonging to family Rubiaceae
• Uses 1. It is used as a flavour in carbonated beverages. 2. It is widely used as an antimalarial agent in tropical countries. 3. It is employed as a skeletal muscle relaxant.
(iii) Acridine Alkaloids
• Biological Source The fresh and dried leaves of Ruta graveolens L. (Rutaceae) (Rue, Garden Rue, German Rue)
• Uses 1. In Chinese medicine rue is considered as an emmenagogue,
hemostat, intestinal antispasmodic, sedative, uterine stimulant, vermifuge, rheumatism, cold and fever.
2. In Poland, it is used as an aphrodisiac and choleretic. 3. The herb is used medicinally as a bitters, an aromatic
stimulant, ecbolic and in suppression of the menses.
Alkaloids Derived from Histidine
• A good number of Pilocarpus species, belonging to family Rutaceae, found to contain plethora of alkaloids with an imidazole ring, namely: pilocarpine, isopilocarpine, and pilosene. It has been observed that the alkaloids in these species invariably reside in the leaves. Pilocarpine constitutes 0.5-1.0% of the dried leaf material. Isopilocarpine appears to vary significantly within a range from 5 to 7.5% of the total alkaloids. Further, the alkaloids are located mostly in the upper epidermal leaves of the cells of the leaves, and also in the cells of the mesophyll bordering upon the lower epidermis.
• The three major alkaloids derived from histidine shall be described in the sections that follows i. Pilocarpine ii.Isopilocarpine iii.Isopilosine
Pilocarpine
• Biological Source Pilocarpine is obtained from the leaves of closely related plants of the genus Pilocarpus, belonging to the natural order Rutaceae. However, the genus comprised of a variety of species commonly known by various names, such as: Pilocarpus jaborandi (Pernambuco Jaborandi), (Pilocarpus pennatifolius (Paraguay Jaborandi); Pilocarpus microphyllus (Maranham Jaborandi); Pilocarpus selloanus (Rio Jaborandi); Pilocarpus trachylophus (Ceara Jaborandi); Pilocarpus spicatus (Aracati Jaborandi); Pilocarpus heterophyllus (Barqui Simento Jaborandi); and Pilocarpus racemosus (Guadeloupe).
• Uses • 1. Pilocarpine possesses miotic and diaphoretic actions. • 2. Pilocarpine nitrate is used extensively as an ophthalmic drug having
cholinergic action. • 3. It is also employed to reduce the intra-ocular pressure in glaucoma
patients.
Isopilocarpine
• Biological Source It is same as pilocarpine
• Uses
1. It is used as an antiglaucoma agent
2. It is also employed as miotic.
Alkaloids Derived from Lysine
• The various alkaloids that are derived from lysine are invariably grouped together under the following categories, namely:
i. Piperidine alkaloids
ii. Quinolizidine alkaloids
iii.Indolizidine alkaloids
(i) Piperidine alkaloids
• Biological Sources It is obtained from the herb and seeds of Lobelia inflata L., (Lobeliaceae) (Indian Tobacco, Asthma Weed); leaves of Lobelia tupa L. (Campanulaceae) (Tupa, Devil’s Tobacco)
• Uses 1. It is widely used as a respiratory stimulant. 2. Its effects resemble those of nicotine and hence used in
lozenges or chewing tablets, containing 0.5-1.5 mg of Lobeline Sulphate, to help in breaking the tobacco habit, otherwise known as ‘smoking deterrants’.
(i) Piperidine alkaloids
• Biological Source It is obtained from the dried unripe fruit of Piper nigrum L. (Black Pepper), Piper longum L., Piper retrofractum Vahl. (Piper officinarum C.D.C.), and Piper clusii C.D.C.; and also in the root bark of Piper geniculatum. Sw. belonging to family Piperaceae.
• Uses 1. It is used as an insecticide. 2. It is also employed extensively as condiment in food
preparations. 3. It is used to give a ‘pungent’ taste to brandy.
(ii) Quinolizidine Alkaloids
• Biological Sources It is obtained from yellow and black lupin beans
Lupinus luteus L., and Lupinus niger Hort.; and also found in Cytisus scoparius (L.) Link. (Fabaceae) (Scotch Broom); Anagyris foetida L., belonging to natural order Leguminosae. Besides, it is also obtained from the roots of Aconitum napellus L. (Ranunculaceae) (Aconite, Monkshood, Blue Rocket); from the herbs of Chelidonium majus L. (Papaveraceae) (Celandine, Great Celandine, Nipplewort); from leaves of Peumus boldus Molina (Monimiaceae) (Boldo).
• Uses 1. It is used mostly as an oxytocic. 2. It is employed as a cardiac depresant, cathartic, diuretic and for
stimulating uterine contractions. 3. Sparteine is used occasionally as a quinidine substitute in
stubborn cases of atrial fibrillation
(iii) Indolizidine Alkaloids
• Biological Source It is obtained from the seeds of the Australian leguminous tree Castanospermum australe A. Cunn. (Leguminosae) (Moreton Bay Chestnut).
• Uses Its has demonstrated activity against the AIDS virus HIV, by virtue of their ability to inhibit glyosidase enzymes involved in glycoprotein biosynthesis. However, the glycoprotein coating seems to be vital for the proliferation of the AIDS virus
Alkaloids Derived from Nicotinic Acid
• The alkaloids derived from the nicotinic acid are commonly known as the ‘Pyridine Alkaloids’. In general, the alkaloids found in tobacco (Nicotiana tabacum, Solanaceae) include a variety of alkaloids, such as: nicotine, anabasine, and niacin (Vitamin B3, nicotinic acid). Interestingly, the ‘pyridine unit’ has its origins in vitamin B3 (nicotinic acid); whereas, a combination of a pyridine ring with a pyrrolidine ring gives rise to nicotine, or a combination of a pyridine ring with a piperidine unit forms anabasine.
(i) Pyridine Alkaloids
• Biological Sources It is widely distributed in nature; and appreciable quantities are found in fish, yeast, liver, and cereal grains
• Uses
1. It is used as antihyperlipoproteinemic agent.
2. It is a vital vitamin (enzyme cofactor).
(i) Pyridine Alkaloids
• Biological Sources It is obtained from the dried leaves of Nicotiana tabacum Linn., (Solanaceae) (Virginia Tobacco; Tobacco); sprouts of Asclepias syriaca L. (Asclepiadaceae) (Common Milkweed); dried leaves and roots of Datura metel L. (Solanaceae) (Unmatal, Metel, Hindu Datura); leaves of Duboisia myoporoides R. Br. (Solanaceae) (Corkwood Tree, Pituri); fresh forage of Equisetum arvense L. (Equisetaceae) (Field Horsetail); herbs of Equisetum hyemale L. (Equisetaceae) (Shavegrass, Great Scouring Rush); leaves of Erythroxylum coca Lam., (Erythroxylaceae) (Coca); fruits and leaves of Nicotiana glauca R. Grah. (Solanaceae) (Tree Tobacco); and leaves of Nicotiana rustica Linn. (Solanaceae)–present upto 2-8%
• Uses 1. It is used extensively as an insecticide and fumigant. 2. It finds its application as a ‘contact poison’ in the form of soap i.e., as its oleate,
laurate and naphthenate salts. 3. It is also used as a ‘stomach poison’ in combination with bentonite. 4. One of its recent applications nicotine is employed as chewable tablets of lozenges
for the treatment of smoking withdrawl syndrome. 5. It possesses a unique action on the autonomic ganglia which it first stimulates and
subsequently depresses ultimately leading to paralysis
Alkaloids Derived from Ornithine
• The various alkaloids derived from ornithine may be categorized into three heads, namely:
(i) Pyrrolidine Alkaloids,
(ii) Tropane Alkaloids, and
(iii) Pyrrolizidine Alkaloids.
(i) Pyrrolidine Alkaloids
• Biological Sources It occurs in the leaves of Erythroxylon coca Lam., (Erythroxylaceae) (Coca); and the roots of Withania somniferum (L.) Dunal. (Solanaceae) (Ashwagandha).
• Uses The drug is broadly used as a sedative, hypnotic laxative and diuretic
(ii) Tropane Alkaloids
• Biological Sources It is obtained from the roots and leaves of Atropa belladona Linn. (Solanaceae) (Belladona); and the seeds and leaves of Datura stramonium Linn. (Syn.: Datura tatula Linn.) (Solanaceae) (Jimson Weed, Thorn Apple, Stramonium), besides other species of Solanaceae, such as: D. metel Linn.; D. innoxia Mill., D. alba Nees.; and D. fastuosa Linn
• Uses 1. It is used in preanaesthetic medication. 2. It is employed as an anticholinergic agent. 3. It is also used as a mydriatic. 4. It is employed as an antidote in opium and chloral hydrate poisoning. 5. It is frequently employed to minimize spasm in cases of intestinal gripping
caused due to strong purgatives. 6. It also find its applications to reduce such secretions as: saliva, sweat, and
gastric juice
(ii) Tropane Alkaloids
• Biological Sources It is obtained from the leaves of Erythroxylon coca Lam. and other species of Erythroxylon, (Erythroxylaceae); and leaves of Erythroxylon truxillense Rusby (Erythroxylaceae).
• Uses 1. It is used as a local anaesthetic as it causes numbness. 2. Its main action is a CNS-stimulant and, therefore,
categorized as ‘narcotic drugs’. It is a highly habit-forming drug.
(ii) Tropane Alkaloids
• Biological Sources It is obtained from the roots and leaves of Atropa bella-dona L. (Solanaceae) (0.21%) (Thorn Apple); fruits, roots and leaves of Datura metel L. (Solanaceae) (Unmatal, Metel, Hindu Datura); leaves and seeds of Datura stramonium L. (Solanaceae) (Jimson Weed, Thorn Apple, Stramonium); root bark of Duboisia myoporoides R. Br. (Solanaceae) (Pituri, Corkwood Tree); young plants of Hyoscyamus niger L. (Solanaceae) (Henbane, Henblain Jusquaime); seeds of Lactuca virosa L. (Asteraceae) (Bitter Lettuce, Wild Lettuce); and the herb Mandragora officinarum L. (Solanaceae) (Mandrake, Loveapple)
• Uses 1. It is mostly employed as an anticholinergic drug. 2. It exerts relaxation of bronchial and intestinal smooth museles (i.e.,
antispasmodic action). 3. It also inhibits contraction of the iris muscle of the eye to produce
mydriasis. 4. It decreases significantly decreases the sweat gland and salivary gland
secretions
(iii) Pyrrolizidine Alkaloids
• Biological Source It is obtained from the herbs of Heliotropium europaeum L. (Boraginaceae) (Heliotrope, Turnsole).
• Uses 1. The plant is used for cancer and is popularly
known as “Herbe Du Cancer” in Europe. 2. It is also used for snakebite and scorpion stings.
(iii) Pyrrolizidine Alkaloids
• Biological Source The hepatotoxic alkaloid is obtained from the whole plant of Senecio vulgaris L. (Compositae); weed of Senecio aureus L. (Asteraceae) (Squaw Weed, Liferoot, Golden Groundsel); and preblooming plant of Tussilago farfara L. (Asteraceae) (Coltsfoot, Coughwort, Horse-Hoof).
• Uses 1. It is used as an excellent drug to control pulmonary
hemorrhage. 2. It is also used to hasten labour and check the pains of
parturition.
Alkaloids Derived from Tyrosine
• There are a number of alkaloids derived from tyrosine which may be classified as stated below:
(i) Phenylethylamine alkaloids,
(ii) Simple Tetrahydro iso-quinoline alkaloids,
(iii) Modified tetrahydro iso-quinoline alkaloids,
(iv) Phenylethylisoquinoline alkaloids, and
(v) Amaryllidaceae alkaloids.
(i) Phenylethylamine alkaloids
• Biological Source It is obtained from the dried latex (opium) by incision from the unripe capsule of Papaver somniferum Linn., (Papaveraceae) to the extent of 0.1-0.5%.
• Uses 1. Narcyl is used as a narcotic analgesic. 2. Narcyl is also employed as an antitussive agent
(i) Phenylethylamine alkaloids
• Biological Sources It is obtained from Peyote (Mescal Buttons) the flowering heads of Lophophore williamsii (Lemaire) Coult. (Coctaceae) and the cactus Trichocereus pachanoi Britton and Rose (Cactaceae) (Achuma, San Pedro Aguacolli).
• Note: This is a controlled substance (hallucinogen) listed in the US code of Federal Regulations
(i) Phenylethylamine alkaloids
• Biological Sources It is obtained from the plant of Lophophora williamsii (Lamaire) Coult. (Catctaceae) (Peyote) and Selenicereus grandiflorus Britt and Rose (Coctaceae) (Night Blooming Cereus).
• Uses It exhibits digitalis-like activity
(ii) Simple Tetrahydro iso-quinoline alkaloids
• Biological Sources It is obtained from the plant Lophophora williamsii (Lemaire) Coult. (Cactaceae) (Peyote), and Anhalonium lewinii. Henn. (Cactaceae).
• Uses It may be used as a mild hallucinogen.
(iii) Modified tetrahydro iso-quinoline alkaloids
• Biological Sources Morphine is obtained from a variety of medicinal plants, such as: Argemone mexicana L. (Papaveraceae) (Prickly Poppy); Eschscholzia californica Cham. (Papaveraceae) (California Poppy); Papaver bracteatum Lindl. (Papaveraceae) (Great Scarlet Poppy; Thebaine Poppy); Papaver somniferum L. (Papaveraceae) (Opium poppy; and Poppyseed Poppy Keshi)
• Uses of morphine 1. It is used as a potent narcotic analgesic. 2. It is usually given in severe pains and also in such instances where patient fails to show
positive response to other analgesics. 3. It exerts a biphasic action on the CNS. 4. It is found to sedate the respiratory centre, emetic centre and the cough centre through its
action in the medulla. 5. It stimulates the chemoreceptor-trigger-zone located in the medulla that ultimately causes
nausea and vomilting; and this is perhaps regarded as a side-effect. 6. It also exerts sedative and hypnotic actions. • Note: Morphine and its salts are habit forming drugs. Hence, its use must be done under
the strict observation of a physician.
Alkaloids Derived from Tryptophan
• The various alkaloids derived from tryptophan are conveniently classified into the following categories, namely: (i) Simple Indole Alkaloids; (ii) Simple β-Carboline Alkaloids; (iii) Terpenoid Indole Alkaloids; (iv) Quinoline Alkaloids; (v) Pyrroloindole Alkaloids; (vi) Ergot Alkaloids.
(i) Simple Indole Alkaloids
• Biological Sources The root bark of Gossypium hirsutum L. (Malvaceae) (American Unplanted Cotton) contains serotonin.
• Uses 1. It is a potent vasoconstrictor. 2. It is also a neurotransmitter in the CNS and is
important in sleep-walking-cycles
(i) Simple Indole Alkaloids
• Biological Sources It is obtained from the sacred mushroom of Mexico known as Teonanacatl. It is also found in the fruiting bodies of Psilocybe maxicana Heim, (Agaricaceae).
• Uses It is a hallucinogenic substance • Note It is a controlled substance listed in the
U.S. Code of Federal Regulations
(ii) Simple β-Carboline Alkaloids
• Biological Sources It is obtained from the bark fruit of Passiflora incarnata L. (Passifloraceae) (May pop, Passion flower); seed of Peganum harmala L. (Rutaceae) (Harmel, Syrian Rue, African Rue), bark of Sickingia rubra (Mart.) K. Schum. (Arariba rubra Mart.), (Rubiaceae); and bark of Symplocus racemosa Roxb. (Symplocaceae).
• Uses It is a narcotic hallucinogen
(iii) Terpenoid Indole Alkaloids
(iii) Terpenoid Indole Alkaloids : coryanthe type
• Biological Sources It is obtained from the plants of Catharanthus lanceus Pichon (Boj.) (Apocynaceae) (Lanceleaf Periwinkle); Catharanthus roseus (L.) G. Don (Apocynaceae) (Periwinkle, Madagascar or Cape Periwinkle, Old Maid]; leaves of Mitragyna speciosa Korth. (Rubiaceae) (Katum, Kutum, Krantum); Rauvolfia scrpentina (L.) Benth. (Apocynaceae) (Rauvolfia, Chandra, Sarpaganda); and bark of Corynanthe johimbe K. Schum., (Rubiaceae).
• Uses 1. It is mostly used as antihypertensive and anti-ischemic agent (both ceretral
and peripheral). 2. It has a broad application in the relief of obstruction of normal cerebral
blood flow.
(iii) Terpenoid Indole Alkaloids : iboga type
• Biological Sources It is obtained in the plant of Catharanthus lanceus Pichon (Boj.) (Apocynaceae) (Lanceleaf Periwinkle); and Catharanthus roseus (L.) G. Don (Apocyanaceae) (Periwinkle, Madagascar or Cape Periwinkle, Old Maid). It is also found in Vinca rosea Linn. (Apocynaceae).
• Uses 1. Its pharmacological action resembles to that of R. serpentina. 2. It also shows beneficial growth inhibition effects in certain human
tumors. 3. It is used as a diuretic.
(iii) Terpenoid Indole Alkaloids
• Biological Sources It is found in the root bark of Alchornea floribunda Muell. Arg. (Euphorbiaceae) (Niando); plant* of Catharanthus lanceus Pichon (Boj.) (Apocyraceae) (Lanceleaf Periwinkle); bark of Pausinystalia johimbe (K. Schum.) (Rubiaceae) (Yohimbe); root of Rauvolfia serpentina (L.) Benth. (Apocynaceae) (Rauvolfia, Chandra, Sarpaganda); and plant of Rauvolfia tetraphylla L. (Apocynaceae) (Pinque-Pinque).
• Uses • 1. It is an aderenergic blocking agent, which has been used extensively in
angina pectoris and arteriosclerosis. • 2. It has been used successfully for the treatment of impotency in patients
with vascular or diabetic problems. • 3. It is invariably employed as a pharmaiological probe for the study of α2-
adrenoreceptor.
(iii) Terpenoid Indole Alkaloids
• Biological Sources It is obtained from the plant Catharanthus roseus (L.) G. Don (Apocynaceae) (Periwinkle, Madagascar or Cape Periwinkle, Old Maid); root of Rauvolfia serpentina (L.) Benth (Apocynaceae) (Rauvolfia, Chandra, Sarpaganda); root of Rauvolfia tetraphylla L. (Apocynaceae) (Pinque-Pinque); and from the plant of Vinca minor L. (Apocynaceae) (Periwinkle).
• Uses 1. It is a hypotensive drug which exhibits strong hypotensive and
sedative activity. 2. It is also employed to alleviate mild anxiety conditions i.e., the drug
shows a mild tranquillizing effect.
(iii) Terpenoid Indole Alkaloids
• Biological Source It is obtained from Vinca rosea Lin.. (Apocynaceae). • Uses 1. The alkaloid is used for the treatment of a wide variety of neoplasms. 2. It is also recommended for generated Hodgkin’s disease, lymphocytic
lymphoma, hystiocytic hymphoma, mycosis fungoides, advanced testicular carcinoma, Kaposi's sarcoma, and choriocarcinoma and lastly the breast cancer unresponsive to other therapies.
3. It is effective as a single entity, however, it is normally given along with other neoplastic agents in combination therapy for the increased therapeutic effect without any noticeable additive toxicity.
4. It arrests mitosis at the metaphase. 5. It is found to be effective in the acute leukemia of children.
(iii) Terpenoid Indole Alkaloids
• Biological Sources It is also obtained from Vinca rosea Lin., (Catharanthus roseus G. Don) belonging to the natural order Apocynaceae
• Uses 1. Vincristine sulphate is recommended for the treatment of acute
lymphocytic leukemia, and in combination therapy in Hodgkin's disease, lymphosarcoma, reticulum cell sarcoma, neuroblastoma, Wilm's tumour and rhabdomyosarcoma.
• Note: Viucristine sulphate being highly unstable; therefore, its refregerated storage in sealed ampules is absolutely essential.
2. It is broadly used as an antineoplastic agent.
(iii) Terpenoid Indole Alkaloids
• Biological Sources It is abundantly found in the seeds of Strychnos Nux Vomica L. (Loganiaceae) (Nux Vomica, Strychnine); beans of Strychnos ignatti Berg. (Loganiaceae); roots of S. cinnamomifolia Thw.; seeds, bark and wood of S. colubrina Linn.; and plant of S. malaccensis Benth. (Syn: S. gautheriana Pierre).
• Uses 1. Strychinine is extremely interesting pharmacologically and is regarded
as a valuable tool in both physiologic and neuroanatomic research. 2. It is extremely toxic, and functioning as a central stimulant. 3. It causes excitation of all parts of the central nervous system and blocks
inhibitory spinal inpulses at the post synaptic level. This may lead to an exaggeration in reflexes ultimately leading to tonic convulsions.
4. The drug is rarely used in modern medical practice but is utilized as a vermin killer i.e., animal or insect killer.
5. It is used chiefly in poison baits for rodents.
(iv) Quinoline Alkaloids
• Biological Sources It occurs in most varieties of cinchona bark as mentioned under quinine (section ‘A’). Besides, cinchonine especially occurs in the bark of Cinchona micrantha R & P. belonging to the natural order Rubiaceae.
• Uses 1. It is used as an antimalarial agent. 2. It is employed as a tonic in waters, bitters and liqueurs. 3. It is broadly used for febrifuge, schizonticide, stomachic,
amebiasis, dysentry, flu, fever, and as a mild stimulant of gastric mucosa.
(iv) Quinoline Alkaloids
• Biological Source Quinidine It is reported to be present in cinchona barks ranging between 0.25-3.0%.
• Uses 1. It is used as an antiarrhythmic agent (Class 1A)*. 2. It finds its applications as an antimalarial drug. 3. It is most commonly employed to treat various cardiac
arrhythmias, namely: atrial flutter, AV junctional and ventricular contractions, atrial and ventricular tachycardia, atrial fibrillation, and premature atrial condition.
Differences Among Four Major Cinchona Alkaloids
(v) Pyrroloindole Alkaloids
• Biological Sources It is obtained from the seeds of Physostigma
venenosum Balf. (Fabaceae) (Calabar Bean, Ordeal Bean) yielding not less than 0.15% of the total alkaloids of physostigma.
• Uses 1. It possesses a cholinergic (anticholinesterase) and miotic activities. 2. It was used earlier to treat myasthenia gravis; but now it is more frequently
used for the eye. 3. It is employed as an antidote for reversing CNS and cardiovascular (viz.,
arrythmia and tachycardia) effects of excessive dosages with tricyclic antidepressants.
4. It helps in the contraction of the ciliary muscle of eye, and a decrease in the intraocular pressure produced by an increased out-flow of the aqueous humor.
5. Physostigmine is employed frequently in ophthalmology to treat glaucoma.
(vi) Ergot Alkaloids
• Biological Sources It is obtained from the seeds of Ipomea
violaceae Linn. (Ipomea tricolor Cav.) belonging to family Convolvulaceae (Morning glory, Tlitliltzen, Ololiuqui); and also from the dried seeds of Rivea corymposa Hall. F. (Convolvulaceae) (Snakeplant).
• Uses 1. Ergonovine is used as an oxytocic. 2. Ergonovine maleate also acts as an oxytocic and produces much
faster stimulation of the uterine muscles as compared to other ergot alkaloids.
3. Methylergonovine meleate is observed to act as an oxytocic whose actions are slightly more active and longer acting than ergonovine.
(vi) Ergot Alkaloids
• Biological Source It is obtained from the seeds of Claviceps purpurea (Fr.) Tul. (Hypocreales) (Ergot).
• Uses 1. It is employed as a potent antimigraine drug. 2. Ergotamine possesses oxytocic properties, but it is not employed for that effect. 3. Ergotamine tartrate is used invariably to prevent or abort vascular headaches,
including migraine and cluster headaches. The mechanism of action is perhaps due to direct vasoconstriction of the dilated carotid artery bed with concomitant lowering in the amplitude of pulsations.
4. Ergotamine tartrate is also an antagonist of the serotonin activity. 5. Ergotamine tartrate is frequently used along with caffeine for the management and
control of migraine headache. Both serve as cerebral vasoconstrictors; while the latter is considered to increase the action of the former.
6. Methylergonovine maleate is an oxytocic reported to be longer acting and more active than ergonovine.
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