1.Tropane Alkaloids Occurrence: - PowerPoint Presentation

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1.Tropane Alkaloids

Occurrence: Atropa, Datura, and Hyoscyamus spp.Main Alkaloids are: 1- Atropine. 2- Hyoscyamine. 3. Hyoscine (Scopolamine).Hyoscyamine is the major natural alkaloid with negative optical rotation (L- form).During extraction hyoscyamine racemizes to the optically inactive DL- Atropine.Both alkaloids composed of tropane base and tropic acid.

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A.

Hyoscine (Scopolamine)Hyoscine is an ester of L-tropic acid with tropane base.Isolation: Japanese belladonna Structure: very similar to that of atropine containing an extra epoxy group.Physiological effect: it inhibits the effect ofacetylcholine on muscarinic receptors.Usage : against intestinal cramping and for motion sickness.

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B.Atropine

Isolation: from deadly nightshade (Atropa belladonna), also inother plants of Solanaceae.Structure: ester of tropane with (+/-) (racemic) tropic acid.The main alkaloid is hyosciamine isomerized to atropine during isolation. Basic compound, used as a salt, sulphate.Physiological effects: parasympatholytic, it inhibits theeffect of acetylcholine on muscarinic receptors.

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Atropine dilate pupils and acts as a spasmolytic of bronchial spasms. Treatment for poisoning by organophosphate insecticides and nerve gases.

Overdose: tachycardia,urinary retention, hallucination, etc.

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C.

HyoscyamineIt is the levorotatory isomer of atropine. is a medication used to treat motion sickness and postoperative nausea and vomiting.[1] It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin after about 20 minutes and last for up to 8 hours

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D.Cocaine

Isolation: Erythroxylon cocaStructure: ester of pseudotropane (stereoisomer of tropane).Cocaine having two ester groups (four chiral centers).Physiological effects: It is considered as psychomotor stimulant for CNS . Euphoria, tacchycardia, hypertension, dyspnea, seizure ,and Arrhythemia.Overdose: respiratory failure, cardiac infarction, ischemia, and hyperthermiaDependency: very strong psychological dependency.

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The drug sends high levels of dopamine into the parts of the brain that control pleasure by blocking the reuptake of this neurotransmitter with serotonin and NE. This buildup causes intense feelings of energy and alertness .

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E.

Pelletierine is an alkaloid from pomegranatPelletierine sulphate is used medicinally in Iraq as an anthelmintic and anti-amoeboid. which is effective against tapeworms, ring worms and nematodes. Simple bark-extracts have recently been shown to be effective in vitro against the intestinal microorganisms salmonella typhi, vibrio cholera, herpes simplex, HIV, and tumors.

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2.Quinoline Alkaloids

Quinine, quinidine, cinchonine, cinchonidine Cinchona spp. (Rubiaceae)

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Quinine administered as free base or salts, continues to be used for treatment of multidrug-resistant malaria, though it is not suitable for prophylaxis. The specific mechanism of action is believed to prevent polymerization of toxic

haemoglobin breakdown products formed by the parasite. Typically, the quinine dosage was up to 600 mg three times a day.

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Quinidine is the principal cinchona alkaloid used therapeutically, and is administered to treat cardiac

arrhymias. It inhibits fibrillation, the uncoordinated contraction of muscle fibres in the heart. It is rapidly absorbed by the gastrointestinal tract and overdose can be hazardous, leading to diastolic arrest.Quinidine, cinchonine, and cinchonidine also have antimalarial properties, but these alkaloids are not as effective as quinine. The cardiac effect makes quinidine unsuitable as an antimalarial.

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3.Indole Alkaloids(benzopyrrole

) More than 3000 terpenoid indole alkaloids are recognized, making this one of the major groups of alkaloids in plants. They are found mainly in eight plant families, of which the Apocynaceae, and the Rubiaceae provide the best sources. ____________________________________________________ 1.Rauwolfia:Rauwolfia is the dried rhizome and roots of Rauwolfia (sometimes Rauvolfia) serpentina (Apocynaceae) or snakeroot, a small shrub from India, Pakistan, Burma, and Thailand.

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Clinical tests showed the drug to have excellent antihypertensive and sedative activity.

It was then rapidly and extensively employed in treating high blood pressure and to help mental conditions, relieving anxiety and restlessness, and thus initiating the tranquillizer.

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Rauwolfia

alkaloidsReserpine & DeserpidineAntihypertensive and AntipsychoticThey act by interfering with catecholamine storage and prevents the transport from cytoplasm to storage vessicle , depleting levels of available neurotransmitters.It acts by blocking the granular catecholamine transport-storage mechanism within the adrenergic neuron. This leads to depletion of catecholamines.

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Ajmaline

& AjmalicineAjmalicine is used as AntihypertensiveAjmaline is used as antiarrhythmic

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2-yohimbine

Yohimbe is the name of an evergreen tree found in parts of central and western Africa.Yohimbe supplements often list yohimbe bark extract or yohimbine as the active ingredient.Yohimbe is taken by mouth arouse sexual excitement, for erectile dysfunction (ED) and for weight loss(fat burner).

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3.Catharanthus

Catharanthus roseus (= Vinca rosea) (Apocynaceae) is a small herb or shrub it is now common in the tropics and widely cultivated as an ornamental for its shiny dark green leaves and pleasant five-lobed flowers. Drug material is now cultivated in many parts of the world, including the USA, Europe, India, Australia, andSouth America.

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Because of its folklore usage as a tea for diabetics, the plant was originally investigated for potential hypoglycemic activity. The selective action suggested anticancer potential for the plant, and an exhaustive study of the constituents was initiated.

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The activity was found in the alkaloid fraction, and more than 150 alkaloids have been characterized in the plant. These are principally

indole alkaloids.the vin- prefix being a consequence of the earlier botanical nomenclature Vinca rosea, which was commonly used at that time. The alkaloids vinblastine and vincristine were introduced into cancer chemotherapy and have proved to be extremely valuable drugs.

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Vinblastine & Vincristine:

Anticancer activityInhibitors of mitosis by binding to protein tubulinpreventing polymerization into microtubules .Despite the minor difference in structure between vinblastine and vincristine, a significant difference exists in the spectrum of human cancers that respond to the drugs. Vinblastine is used mainly in the treatment of Hodgkin’s disease, a cancer affecting the lymph glands, spleen, and liver.

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Vincristine has superior

antitumour activity compared to vinblastine but is more neurotoxic. It is clinically more important than vinblastine, and is especially useful in the treatment of childhood leukaemia, giving a high rate of remission. Some other cancer conditions, including lymphomas, small cell lung cancer, and cervical and breast cancers, also respond favorably. The alkaloids need to be injected, and both generally form part of a combination regimen with other anticancer drugs.

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Vindesine

is a semi-synthetic derivative of vinblastine, which has been introduced for the treatment of acute lymphoid leukaemia in children.These compounds all inhibit cell mitosis, acting by binding to the protein tubulin in the mitotic spindle, preventing polymerization into microtubules, a mode of action shared with other natural agents, e.g. colchicine.A major problem associated with the clinical use of vinblastine and vincristine is that only very small amounts of these desirable alkaloids are present in the plant. Although the totalalkaloid content of the leaf can reach 1% or more, over 500 kg of catharanthus is needed yield 1 g of vincristine.

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Vindesine

& VinorelbineSemisynthetic derivatives of VinblastineAnticancer activity Unlike other vinca alkaloids, the catharanthine unit is the site of structural modification Inhibitors of mitosis by binding to protein tubulin preventing polymerization into microtubules .

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4.Claviceps

purpurea. (Hypocreaceae)A/Ergonovine (Ergometrine) .This alkaloid is a potent oxytocic: it increases basal tone, and the frequency and strength of uterine contractions; the more advanced the pregnancy, the stronger the effect is.

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This activity is thought to be linked to the stimulation of the α-adrenergic receptors in the myometrium .

Uterine hypertonicity is at the origin of the antihemorrhagic effects of ergonovine. In practice, methylergonovine is the preferred medication.

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Ergometrine

stimulates contractions of uterine and vascular smooth muscleFollowing administration of usual therapeutic doses of ergometrine, intense contractions of the uterus are produced and are usually followed by periods of relaxation.

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B /Ergotamine

1-Ergotamine is used in the treatment of acute attacks of migraine, 2- Ergotamine is effective orally, or by inhalation in aerosol form, and may be combined with caffeine for treatment of migraine.At low doses, ergotamine is a potent vasoconstrictor acting by stimulation of the α-adrenergic receptors .

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The change in vascular tone is particularly marked peripherally and in the branches of the external carotid; this reaction is accompanied by the closure of the

arterio-venous shunts. At higher doses, an adrenergic antagonist activity appears, which is weak, and illustrates the duality in the activities of this compound. In addition, ergotamine is an oxytocic.

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6.Physostigmine:

Physostigma venenosumA cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.

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Physostigmine

(also known as eserine) is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor.

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Physostigmine

(eserine) is a reversible inhibitor of cholinesterase, preventing normal destruction of acetylcholine and thus enhancing cholinergic activity. Its major use is as a miotic, to contract the pupil of the eye, often to combat the effect of mydriatics such as atropine. It also reduces intraocular pressure in the eye by increasing outflow of the aqueous humour, and is a valuable treatment for glaucoma, often in combination with pilocarpine

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Because it prolongs the effect of endogenous acetylcholine, physostigmine

can be used as an antidote to anticholinergic poisons such as hyoscyamine/atropine and it also reverses the effects of competitive muscle relaxants such as curare, tubocurarine, atracurium.

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Anticholinesterase drugs are also of value in the treatment of Alzheimer’s disease, which is characterized by a dramatic decrease in functionality of the central cholinergic system. Use of

acetylcholinesterase inhibitors can result in significant memory enhancement in patients, and analogues of physostigmine are presently in use (e.g. rivastigmine) or in advanced clinical trials (e.g. eptastigmine). These analogues have a longer duration of action and less toxicity than physostigmine.

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Synthetic analogues

Synthetic analogues of physostigmine which have been developed retain the carbamate residue, an aromatic ring to achieve binding and to provide a good leaving group, whilst ensuring water-solubility through possession of a quaternary ammonium system. Neostigmine, pyridostigmine, and distigmine are examples of synthetic anticholinesterase drugs used primarily for enhancing neuromuscular transmission in the rare autoimmune condition myasthenia gravis, in which muscle weakness is caused by faulty transmission of nerve impulses.