Purine alkaloids and Protoalkaloids By Noor Hisham AlAtraqchi

Purine alkaloids and Protoalkaloids By: Noor Hisham Al-Atraqchi MSc pharmacognosy

Purine alkaloids The purines are consisting of a six-membered pyrimidine ring fused to a five-membered imidazole ring. three well-known examples are : n Caffeine (1, 3, 7 -trimethylxanthine), n Theophylline (1, 3 -dimethylxanthine) n Theobromine (3, 7 -dimethylxanthine). Botanical origin: § Coffea arabica § Cola nitida § Theobroma Cocoa seeds Tae leaves (camilla sinensis) § xanthine

Coffee bean or seed is the dried ripe seed of coffea arabica and other variation. Constituents Coffee seed contain : • 1 – 2 % caffeine • 0. 25 % trigonellin • 3 – 5 % tannin. • 15% glucose and dextrin • 10 – 13 % fatty oil. The action of coffee depends principally on the caffeine which acts on central nervous system, kidneys, muscles and the heart.

Cola, Kola kola nut is the dried cotyledon of cola nitida or other species (F. sterculiaceae). n Kola nuts contain caffeine up to 3. 5% and 1 % of theobromine. Uses: n Kola posse central stimulant action of caffeine. n Principal use is in manufacture of nonalcoholic carbonated beverages n

Cocoa seed n n Cocoa seeds (Cocoa Beans) are obtained from Theobroma cacao (Sterculiaceae), a tree usually 4 -6 m high. Cocoa is produced in South America, Central America, the West Indies, West Africa. Constituents: n n n Cocoa seeds contain 0. 9 -3. 0% of theobromine The seeds also contain 0. 05 -0. 36% caffeine, cocoa fat or butter. The fresh seeds contain about 5 -10% of water-soluble polyphenols (epicatechol, leucoanthocyanins and anthocyanins)

Tea: Is prepared leaves and leaf bud of camellia sinensis (F. theaceae). constituents : § 1 -4 % caffeine, § small amount of theobromin, theophyllin and xanthine, § 15% gallotannic acid § 0. 75 % volatile oil. The stimulation action is due to caffeine content.

Caffeine: 1, 3, 7 -trimethyl xanthine occur in coffee, tea, cacao and kola usually prepared from tea or recovered from coffee roasters.

Pharmacological Activity of Caffeine n 1. 2. 3. n n 1. 2. 3. 4. CNS stimulant activity: Enhances alertness, Facilitates thought formation, Decreases the sensation of fatigue. Stimulates respiratory centre of the brain (increasing sensitivity to CO 2). Cardiovascular activity: Positive inotropic action, tacchycardia, slight peripheral dilation, mild diuretic action

Caffeine: Uses n n In combinations with antipyretics and analgesics, cold and flu medication. To increases the intestinal absorption of some of these drugs; or to counteract drowsiness. Ingredient in non-alcoholic beverages and “energizing” beverages

Side effects of caffeine Sinus tacchycardia Epigastric pain Nausea Vomiting Nervousness Insomnia tremors

Theophylline or 1, 3, -dimethyl xanthine. Pharmacological Action of Theophylline: § Bronchial smooth muscle relaxant § Stimulates respiratory center in the brain stem by increasing sensitivity to CO 2. § CNS stimulating § Slightly inotropic. § Diuretic activity is stronger than that of caffeine.

Uses: Theophylline utilized principally as smooth muscle relaxants for : • The symptomatic relief or prevention of bronchial asthma. • Treatment bronchospasm associated with chronic bronchitis and emphysema • Cough & reversible bronchospasm (chronic obstructive pulmonary disease)

Theobromine 3, 7 -dimethyl xanthine obtained from dried ripe seed of theobroma cacao ( F. strerculiaceae ) uses § Cocoa has nutritive, stimulant and diuretic properties. § Theobromine is used as a diuretic. . § It has less action on the CNS than caffeine. § Oil of theobroma is used in pharmacy chiefly as a suppository base.

Protoalkaloids, Phenylalkylamines, Biological amines

Protoalkaloids • The alkaloids in this group do not contain heterocyclic nitrogen atoms. • Many of them are simple derivatives of phenyl ethyl amine. • They are not restricted to any particular class of alkaloids and are often classified according to the amino acids from which they are derived. • The drugs and their alkaloids classified as alkaloidal amine are: Ephedra ephedrine, pseudoephedrine Colchicum corm colchicine Khat cathinone

Ephedra n n n Various species of Ephedra (Ephedraceae) are used as a source of the alkaloids ephedrine and pseudoephedrine, which may also be prepared by synthesis. Among these are the Chinese species Ephedra sinica. Ephedra used as remedy for Asthma in Chinese medicine. Ephedrine has two stereogenic (chiral) centres and, therefore, has four possible isomers. (-)-Ephedrine is the major Alkaloid in Ephedra. Ephedrine is a phenylalkylamine with N atom in the side chaine

Actions: Ephedrine is potent sympathomimetic similar to adrenaline that stimulates adrenergic receptors. Mechanism of action: It excites the sympathetic nervous system, causes, vasoconstriction and cardiac stimulation and produce effect similar to those of Epinephrine. It produces rise in blood pressure and causes mydriasis.

Uses: The drug present as Ephedrine sulfate used: n To treat hypotensive states. n For local treatment of nasal congestion n For allergic disorders as bronchial asthma and hay fever n Its action is more prolonged than that of adrenaline, and it has the further advantage that it need not be given by injection but may be administered by mouth.

Colchicum seed: Is the dried rips seed of colchicum autumnale (F. Liliaceae). Colchicum corm is the dried corm of the same species. Colchicum contains the alkaloid colchicine which is 0. 8 % in the seed and 0. 1% in corm. Uses • Colchicine is use in the treatment of gout by decease deposition of uric acid and decrease inflammatory response. • The alkaloid is also used in biological experiments to produce polyploidy or multiplication of the chromosomes in a cell nucleus

Khat n n n This consists of the fresh leaves of Catha edulis (Celastraceae). The plant is cultivated in parts of east and southern Africa, and in southern Arabia. Its traditional use is similar to that of coca in that the fresh leaves, when chewed, have a stimulatory effect with the alleviation of depression and of the sensations of hunger and fatigue.

Khat contains a potent phenylalkylamine alkaloid ( - ) Cathinone has pharmacologic properties similar to amphetamine, and is of similar potency with a similar mechanism of action. They induce catechol amine release from storage site, so it cause euphoria and habit formation.

Khat – Uses and Actions § Traditionally: Fresh leaves are chewed and used to elevates mood, increases mental and physical activity § Used by students & labourers. § Used to treat depression (brings about a sense of well-being) § Alleviates sensations of hunger and fatigue. § CNS stimulant activity § Abused drug