TROPANE ALKALOIDS AND STEROIDAL ALKALOIDS Mosul UniversityCollege of

TROPANE ALKALOIDS AND STEROIDAL ALKALOIDS Mosul University/College of Pharmacy By : Noor Hisham Al –Atraqchi M. Sc. pharmacognosy

TROPANE ALKALOIDS The parent base is the “Tropane” base which is a dicyclic compound formed by the condensation of pyrrolidine precursor (ornithine) with piperidine ring. They are ester alkaloids resulted from the coupling of organic acids tropic acid with alcoholic base tropanol. Tropic acid Tropanol

• They are found mainly in Solanaceae family , but also in Erythroxylaceae. • The principal alkaloids of medicinal interest in this group are: 1 - Hyoscyamine; 2 -Atropine, 3 - Hyoscine (scopolamine). 4 - Cocaine • 1. 2. 3. 4. These alkaloids found in the following plants : Atropa Belladonna Hyoscyamus species, Datura stramonium. Coca

Symesynthetic derivatives, e. g. hyoscine butylbromide are of medical importance.

Atropine: Is an alkaloids obtained from atropa belladonna, datura sp. and hyoscyamus sp. F. (solanaceae) or produced synthetically. It is extremely poisonous. Action and uses : Atropine is a cholinergic blocking agent , occupying the postsynaptic receptor sites , preventing the normal neurotransmitters from acting, so atropine have the following effects: • Antispasmodic, it relax the smoothe muscle of intestine • Medriatic, cause mydriasis when apply directly on the pupil of eye and used in the ophthalmology during examination of eye. • Atropine sulfate is an anticholenergic used in surgery to control bronchial, nasal pharyngeal and salivary secretions. • Atropine has a stimulant action on the central nervous system • Atropine is an antidote to poisoning with eserine(physostigmine), pilocarpine , newstigmine and organophosphorous insecticides.

Hyoscyamine Is the tropine ester of (-) tropic acid. When (-) hyoscyamine is extracted from the plants in which it occur, it is usually racemized during the process and thus converted into (+ ) compound which is atropine. Hyoscyamine sulfate is sulfate of an alkaloids obtained from hyoscyamus or other genera of solanaceae. It is extremely poisonous. Uses: Hyoscyamine sulfate is an anticholinergic, and also has been used to treat acute arrhythmias Hyoscyamine used to control gastric secretion, Decrease motility of smooth muscles so used as antispasmodics. e. g: in abdominal cramps. In Parkinsonism used to reduce rigidity and tremors. Drug in pharmacy: tablets, capsules, oral drops and injection.

Scopolamine: or hyoscine § An alkaloids that is particularly abundant in Datura species. § Hyoscine is an ester of l-tropic acid with scopoline base § It is the epoxide derivative of hyoscyamine.

USES OF HYOSCINE ( SCOPOLAMINE) o Scopolamine hydrobromide is classified as an anticholinegic at usual therapeutic doses. o Hyoscine lacks the central stimulant action of atropine; it has sedative properties and employed in preoperative medication, for preanesthetic sedation. o Hyoscine is mainly used as antiemetic in the control of motion sickness. o Atropine and hyoscine are used to large extent in ophthalmic practice to dilate the pupil of the eye.

SIDE EFFECTS OF TROPANE ALKALOIDS Dry mouth Headache Nervousness Dizziness Drowsiness Palpitation Tachycardia Blurred vision Mydriasis Urinary retention Nausea and vomiting

STRAMONIUM LEAF It consist of the dried leaves or dried flowering tops of Datura stramonium and its varieties (Solanaceae). The generic name, Datura, is derived from the name of the poison, Dhat, which is prepared from Indian species.

Stramonium usually contains 0. 2 -0. 45% of alkaloids, the chief of which are hyoscyamine and hyoscine, but a little bit atropine may be formed from the hyoscyamine by racemization. At the time of collection these alkaloids are usually present in the proportion of about 2 parts of hyoscyamine to 1 part of hyoscine, but in young plant hyoscine is the predominant alkaloid. Stramonium seeds contain about 0. 2% of mydriatic alkaloids and about 15 -30% of fixed oil.

ATROPA BELLADONNA (DEADLY NIGHTSHADE) Belladonna leaf consists of the dried leaves and, occasionally fruitbearing flowering tops of Atropa belladonna (Solanaceae). In the USA the plant is often known as the ‘Poison Black’. The drug obtained from Atropa belladonna contains 0. 3 -0. 6% of alkaloids, the chief of which is hyoscyamine. The generic name of the plant is referred to atropos, the ancient Greek Fate who, in mythology, cut the thread of life. And belladonna, meaning beautiful lady in Italian and refers to the use of juice of the berries of this plant by ladies in 16 th century to dilate the pupils of their eyes which was considered attractive feature.

Uses • Belladonna act as a parasympathetic depressant which account for it is use as spasmolytic agent. • Belladonna leaves are mainly used as sedatives and to check secretion. • The drug is used as adjunctive therapy in the treatment of peptic ulcer and other functional digestive disorders. • Due to anticholinergic property , it is used to control excess motor activity of the GIT and spasm of urinary tract.

HYOSCYAMUS NIGER Hyoscyamus (Henbane) consists of the dried leaves and flowering tops of Hyoscyamus niger (Solanaceae). Hyoscyamine and hyoscine are the principal alkaloids. It is required to contain not less than 0. 05% of total alkaloids calculated as hyoscyamine. Henbane resembles belladona and stramonium in action but is somewhat weaker. The higher relative proportion of hyoscine in the alkaloid mixture makes it less likely to give rise to cerebral excitement than does belladona. It is often used to relieve spasm of the urinary tract.

COCA LEAF AND COCAINE Coca leaves are derived from cultivated shrubs called Erythroxylum coca (Erythroxylaceae). By employing the alkaloid in ophthalmic surgery in 1884 Carl Koller was the first to introduce it into clinical practice. Cocaine is methyl ester of benzoyl ecgonine. When hydrolyzed it splits into ecgonine, benzoic acid and methyl alcohol.

CONSTITUENTS AND USES OF COCA Coca leaves contain about 0. 7 -1. 5% of total alkaloids, of which cocaine, cinnamyl cocaine and α-truxilline are the most important. Cocaine and its salts were the earliest of the modern local anesthetics but, because of their toxic and addictive properties, their use is now almost entirely confined to ophthalmic, ear, nose and throat surgery, and in the control of severe pain for patients with terminal cancer. Cocaine HCl is a local anesthetic and it is applied topically to mucous membrane as 1 – 4 % solution.

The leaves are extensively chewed to relief stress and fatigue. Chemical structure of cocaine has led to several synthetic anesthetics e. g. procaine. Cocaine is highly addictive and agent of abuse, it is generally inhaled or sniffed and rapidly absorbed across the pharyngeal mucosa; resulting in cerebral stimulation and euphoria in addition they are injected IV and S. C. while cocaine base free is smoked.

STEROIDAL ALKALOIDS

STEROIDAL ALKALOIDS Steroidal alkaloids are the alkaloids with steroidal nucleus and Natom. Steroidal nucleus refers to the carbon skeleton of four rings (cyclo pentano per hydro phenanthrene ring). They are either formed from cholesterol or from cholesterol precursor. N- atom in the alkaloids may be in closed ring or as side chain substituent. These group of alkaloids invariably occur in the plant kingdom as Glycosidal combination with carbohydrate moieties, therefore are known as “Glycoalkaloids”. The important plants and their alkaloids are e. g. Solanum and Veratrum alkaloids

1 - SOLANUM ALKALOIDS Occurrence: They occurs in Solanum spp. Consitituents: Solanine, Solasonine. Properties: They are glucoalklaloids with a sugar parts. Uses: 1 - The aglycone of both alkaloids are used as a starting material for the synthesis of steroidal drugs. 2 - Solasonine is used as agricultural insecticide.

2 - VERATRUM ALKALOIDS The important plants and their alkaloids are veratrum viride and veratrum album. They contains a complex mixture of ester alkaloids, glycoalkaloids and alkamines. Two ester alkaloids: proveratrine A and B are the most active. Actions and Uses 1) Hypotensive properties. 2) Used as insecticides Proveratrine A