Dr.Hussam Pharmacognocy Lec: 2 Pyridine Piperidine Alkaloids

Lec: 2 pharmacognocy Dr.hussam

The alkaloids in this group contain Pyridine or Piperidine in the molecule. The important alkaloids in this group are Nicotine, Coniine, Arecoline, Lobeline etc.

Drugs containing pyridine_piperidine Alkaloids:

1-Lobelia or (Indian tobacco): is the dried leaves & tops of Lobelia inflata F: Lobeliaceae. The drug contains 14 alkaloids, of which lobeline is the major & most important.

Lobeline: (-)-lobeline or alpha lobeline: Similar but weaker pharmacological effects to those of nicotine on the peripheral circulation, neuromuscular junctions, and CNS. For this reason, Lobeline sulphate was formerly incorporated in chewing tablets or lozenges that were intended to aid in breaking the tobacco habit (smoking deterrents). Lobeline had placebo effect on decreasing the physical craving for cigarettes.Traditionally used by the Native Americans for asthma& Chronic bronchitis(respiratory stimulant) .Injection of lobeline hydrochloride is used in the resuscitation of newborn infants.

2-Areca, Areca nut or Betel Nut:

Is the dried, ripe seed of Areca catechu (F. Palmaceae). It is rich in group of alkaloids mainly nicotinic acid derivatives:

1-arecoline 2-arecaidine

Lec: 2 pharmacognocy Dr.hussam

3-guvacine 4-guvacaline (guvacin methyl ester)

It is derived from aspartic acid & glycerol. It was used as anthelmintic in veterinary practice and is employed as taenifuge & vermicide.

3-Tobacco: is the dried leaf of Nicotiana tabacum F: Solanaceae. It is cultivated for smoking, it contains alkaloids from 0.6-0.9%.the importance of them is nicotine which is an oily liquid alkaloid, it is colorless liquid but when oxidized convert to yellow color.

Nicotine: in small doses can act as respiratory stimulant, but in large dose it causes respiratory depression. It is a ganglionic (nicotinic) cholinergic receptor agonist. The free base is more toxic than its salt; nicotine is toxic to human due to its effect on nervous system. Recent studies suggest that nicotine can improve memory (reduces risk of Alzheimer) by stimulating the transmission of nerve impulses. Generally, it is used as antiseptic. Nicotine is a toxic alkaloid & a dose of 40mg is said to be fatal to humans. Death results from respiratory paralysis. The average cigarette may contain 10-14mg of nicotine & a cigar about 70mg & much attention has focused on the relationship among lung cancer, smoking & nicotine. However nicotine has pronounced effects on the cardiovascular system, where peripheral vasoconstriction, atrial tachycardia & an increase in both systolic & diastolic blood pressure are observed. It is worth noting that 50% of all smokers die of heart disease & 20% of lung cancer. The carcinogenicity of tobacco is probably not due to nicotine but rather to a far more potent carcinogen (N-nitroso nornicotine). It is found in cigarettes, cigar& chewing tobacco at levels in the range of 2-90 ppm. The carcinogenicity of N-nitroso nornicotine derivatives is well known & considered hazardous to health.

Note: chronic use of nicotine may result in psychological and physical dependence. As a temporary aid for the cessation of cigarette smoking, the drug is available in transdermal patch and it is also available bound to an ion exchange resin in a chewing gum base. These alternative sources

Lec: 2 pharmacognocy Dr.hussam of nicotine help reduce the withdrawal symptoms associated with nicotine addiction.

Nicotine N-nitroso nor nicotine

Biosynthesis of nicotine:

Nicotine is biosynthesized from ornithine +aspartic acid+ glyceraldehyde.

4-Pomegranate: it is the fruit or fruit rind or bark of stem of Punica granatum F: Punicaceae

It contains many alkaloids namely:

Pelletierine Pseudo Pelletierine It is used as anthelmintic. It is biosynthesized from lysine & acetate group.

5- Conium or poison Hemlock:

It is the full grown but unripe fruit of Conium maculatum

F: Umbellifareae.

It contains number of alkaloids, the important of which are Coniine& Conhydrine

Lec: 2 pharmacognocy Dr.hussam

Coniine Conhydrine It is used as antispasmodic and sedative; it is synthesized from lysine and two acetyl molecules. Coniine is very poisonous, lethal dose 120-300 mg, death may occur after ½ hr (or may prolonged to 3 –12 hrs).

2-Tropane alkaloids:

Tropane is a dicyclic compound formed by the condensation of a pyrrolidine precursor (ornithine) with 3 carbon atoms derived from acetate. Both pyrrolidine and piperidine ring system can be recognized in the molecule. The 3-hydroxy derivative of tropane is known as tropine.it is esterification with (-) – tropic acid yields hyoscyamine (tropine- tropate) which may racemized to form atropine.

Biosynthesis of tropane alkaloids: because of the commercial importance of hyoscyamine & scopolamine, investigation of their biosynthesis has been extensive, especially in Datura species. Feeding studies with labeled ornithine have revealed that this amino acid is incorporated to form the pyrrolidine ring of tropine. The remaining 3 carbon atoms are derived from acetate & thus complete the piperidine

Lec: 2 pharmacognocy Dr.hussam moity. Methylation results via transmethylation from methionine to complete the tropine nucleus. On the other hand from phenylalanine, tropic acid is formed via rearrangement and other reactions. Esterification of tropine and tropic acid results in the formation of Hyoscyamine and thus other Tropane alkaloids are synthesized.

The (-) isomer is hyoscyamine , the (+) isomer is not found in the plant ,(±) isomer is the atropine. Hyoscyamine is more active than atropine. Hyoscine is an epoxide of atropine & it is the (-) isomer. The (±) isomer of scopolamine is atrosine. When (-) hyoscyamine is extracted from the plants in which it occurs, it is usually racemized during the process & thus converted to the (±) compound which is atropine. Semisynthetic

Lec: 2 pharmacognocy Dr.hussam derivatives ex. Hyoscine N-butylbromide (buscopane) is of medicinal importance.

Drugs containing alkaloids:

1-Belladonna leaf (deadly nightshade leaf): two parts are official, the root & the leaf. It is the dried leaf or root of Atropa belladonna F: Solanaceae.The root is richer than the leaf in alkaloids. Most of the alkaloids found is hyoscyamine , hyoscine(scopolamine) & traces amount of atropine base.

Uses and Doses:

Belladonna acts as antimuscarnic agent which accounts for it's use as spasmolytic drug, it used as adjunctive therapy in the treatment of peptic ulcer, functional digestive disorders including ulcerative colitis, diarrhea & pancreatitis also it has anticholinergic properties so it used to control of spasm of the urinary tract. Also it dilates the pupil; it is therefore a parasympatholytic & mydriatic.

Belladonna leaf is commonly administered in form of the belladonna tincture; the usual dose of the tincture is 0.6ml t.i.d. (30mg alkaloids/100ml).

2-Hyoscyamus or henbane: dried leaves & flowering tops of Hyoscyamus niger F: Solanaceae.it contains 0.04% of total alkaloid calculated as hyoscyamine. Also contains hyoscine & traces of atropine.

3-stramonium:

Solanaceous alkaloids:

The principle alkaloids of this group are hyoscyamine, atropine and scopolamine(hyoscine)

1- Atropine: used as a mydriatic, also used as antidote in cases of poisoning caused by organophosphate insecticides, it has antisecretory effect used to reduce respiratory secretion & gastric secretion. 2- Scopolamine : it has a depressant activity on the central nervous system and is used to treat motion sickness(prevent nausea and vomiting)

Lec: 2 pharmacognocy Dr.hussam

3- Hyoscyamine: is anticholinergic, it is used to aid in the control of gastric secretion, visceral spasm also it reduces rigidity and tremor in Parkinsonism.

Note: at usual therapeutic doses, scopolamine is a central nervous depressant whereas atropine is a stimulant. For this reason, scopolamine hydrobromide is used for preanesthetic sedation in conjunction with analgesics.

4-Cocaine: it is a habit forming drug from the leaves of Erythroxylum coca F: Erythroxylaceae. The plant is also called coca or coca leaves. coca contain 3 types of alkaloids:

1-dervaitives of ecgonine (Cocaine, cinnamylcocaine, α&β- truxilline)

ecgonine

2-Pseudotropine (tropacocaine,valerine) 3-Hygrine(hygroline , cuscohygrine)

Only the ecgonine derivatives are commercially important. The most important of these alkaloids is cocaine.

Cocaine is the methyl ester of benzoylecgonine. When hydrolyzed, it splits into ecgonine, benzoic acid & methyl alcohol. Cocaine & cocaine HCl as agents of abuse are generally inhaled or sniffed& are rapidly absorbed across the pharyngeal mucosa resulting in cerebral stimulation & euphoria. Cocaine HCl is a local anesthetic. It is applied topically to mucous membrane as 2-5% solution. Cocaine HCl is an ingredient in Brompton's cocktail, which is widely used to control sever pain associated with terminal cancer. Because of it is CNS stimulant properties, cocaine counteracts the narcotic induced sedation &

Lec: 2 pharmacognocy Dr.hussam respiratory depression associated with the narcotic analgesic ingredient (morphine or heroin) used in the cocktail.it also potentiate the analgesic effect. In continuous use, they are narcotics.

Coca leaves have long been chewed by the South American, Indians to prevent hunger & to increase endurance.

5-Withania: is the dried root of Withania somnfera F: Solanaceae. Recent studies have shown that withania which is closely related botanically to Belladonna & Hyoscyamus contains about a dozen of alkaloids e.g. tropine, pseudotropine, hygrine, cuscohygrine, anaferine (two piperidine moieties)

The end

Dr. Hussam H. Sahib