H

Cocaine

Senecio Alkaloids. Senecio alkaloids possess a pyrroli-zidine nucleus and occur in the genera Senecio (Composi-tae), Heliotropium and Trichodesma, and Crotalaria. They are biosynthetically derived from two units of ornithine in a manner similar to some of the lupin alkaloids. Certain of the alkaloids having an unsaturated nucleus are potent hepatotoxins.

Nicotine. Nicotine is toxic, soluble in water, and a constituent of tobacco. The lethal human dose is ca 40 mg/kg. Pharmacologically, there is an initial stimulation followed by depression and paralysis of the autonomic ganglia. The biosynthesis of nicotine is well established.

Nicotine

Lysine-Derived Alkaloids

Lysine-derived alkaloids contain the pyridine nucleus or its reduced form, piperidine. They include alkaloids derived from the Areca or Betel nut, Lobelia alkaloids, and those derived from pomegranate or club mosses.

Arecoline, a colorless liquid alkaloid that has a pronounced stimulant action (in large doses, paralysis may occur) is found in the Areca or Betal nut. As the hydro-bromide it is used as a diaphoretic and anthelmintic.

Lobelia inflata, known as Indian tobacco, contains lobeline, which is similar to, but less potent than, nicotine in pharmacologic action and is used as an emetic; the sulfate salt is used in antismoking tablets.

The root of Púnica granatum contains alkaloids such as pelletierine and pseudopelletierine, which are formed from lysine and acetate. Pelletierine, is toxic to tapeworms and is used as an anthelmintic.

The club mosses, Lycopodium spp., produce polycyclic alkaloids such as lycopodine, whereas Hydrangea spp. yield febrifugine, an active antimalarial agent. Anabasine is found in Haloxylon persicum Bunge; this alkaloid has antismoking and respiratory muscle stimulation action similar to lobeline and is also used as a metal anticorro-sive.

A host of complex alkaloids such as lupinine, sparteine, cytisine, and matrine are found in the lupins, a large plant family of the Leguminosae. Sparteine paralyzes motor nerve endings and sympathetic ganglia. The sulfate is used as an oxytoxic and the adenylate derivative is used to treat cardiac insufficiencies. Cytisine, found in the seeds of the highly toxic plant Cytisus laburnum L., is a strongly basic alkaloid that produces convulsions and death by respiratory failure.

CH2OH

CH2OH

Pelletierine

Nicotine

Pelletierine

Anthranilic Acid-Derived Alkaloids

Anthranilic acid-derived alkaloids exhibit great structural diversity. This group includes dictamnine, platydesmine, vasicine, cusparine, and rutecarpine. Vasicine has oxytocic activity.

Phenylalanine- and Tyrosine-Derived Alkaloids

Phenylalanine- and tyrosine-derived alkaloids are by far the most numerous group of alkaloids, ranging from simple phenethylamines to the very complex dimeric benzyl-isoquinolines and the highly rearranged Cephalotaxus alkaloids.

Ephedrine. Ephedrine, from the Chinese drug Ma Huang, is soluble in water, alcohol, chloroform, and diethyl ether. It melts over the range of33-42°C, depending on the water content. Little of the ephedrine of United States commerce is obtained from natural sources. Ephedrine is produced commercially through a biosynthetic process. Ephedrine has mydriatric effects and demonstrates adrenaline-like activity. It causes a rise in arterial blood pressure, increased secretions, and dilated pupils; it is a monoamine oxidase inhibitor and is used in nasal decongestants.

Peyote. Peyote, the small cactus of the Indians of north central Mexico, contain over 60 constituents. It is used as a hallucinogen in religious ceremonies and for medicinal purposes. A principal constituent is mescaline, a simple trimethoxyphenethylamine.

OCH3 Mescaline

OCH3 Mescaline

Ipecac. Ipecac, derived from Cephaelis ipecacuanha (native to Brazil), contains emetine and cephaeline, both of commercial significance. Emetine exhibits profound pharmacologic effects including clinical antiviral activity and is used in the treatment of amebic dysentery. Its side effects are cardiotoxicity, muscle weakness, and gastrointestinal problems including diarrhea, nausea, and vomiting. Two synthetic routes to emetine are of commercial importance: the Roche synthesis, which produces dehy-droemetine, and the Burroughs-Wellcome synthesis. In handling emetine and its products, exposure should be limited as it can cause severe conjunctivitis, epidermal inflammation, and asthma attacks in susceptible individuals.

Isoquinoline and Related Alkaloids

Isoquinoline and related alkaloids are the largest group of alkaloids derived from phenylalanine (or its hydroxylated derivatives) and corresponding /i-phenylacetaldehydes. The alkaloids are prevalent in the plant families Fumari-aceae, Papaveraceae, Ranunculaceae, Rutaceae, and Ber-beridaceae. There are many structural types, including the simple tetrahydroisoquinolines; the benzylisoquinolines; the bisbenzylisoquinolines, such as the dl- and (¿-isomers of tetrandrine, which exhibit anticancer activity; the pro-aporphines, such as glaziovine, which is an antidepressant; the aporphines, such as glaucine; the aporphine— benzylisoquinoline dimers, such as thalicarpine, which shows cytotoxic and antitumor activity; the oxoaporphines; the protoberberines, a group of over 70 alkaloids such as xylopinine, berberine, canadine, and corydaline, known for such diverse pharmaceutical uses as tranquilizers, CNS depressants, antibacterial and antiprotozoal agents, anticancer agents, and alpha adrenergic blockers; the benzo-phenanthridines, a group of 30 alkaloids such as fagaro-nine and nitidine, which exhibit antitumor properties; the protopines; the phthalideisoquinolines, a group that includes narcotine, which possesses antitussive activity, depresses smooth muscles, and is not narcotic, and hydra-stine, which is used as an astringent in mucous membrane inflammation; and the homoaporphines.

The Opium Alkaloids

The opium alkaloids number over 25, some of which are of commercial importance and major significance. Opium is the air-dried milky exudate from incised, unripe capsules of Papaver somniferum L. or P. albumen Mill (Papaveraceae). Notable opium-derived alkaloids include morphine, codeine, thebaine, noscapine, and papaverine.

Morphine is the most important alkaloid. It is isolated from opium. Along with its salts, it is classified as a narcotic analgesic and is strongly hypnotic. Side effects include constipation, nausea, and vomiting in addition to habituation, reduced power of concentration, and reduction in fear and anxiety. Respiration is also deepened.

Codeine is the methyl ether of morphine, and thebaine is one of the methyl enol ethers of codeinone. Codeine pharmacologically resembles morphine but is weaker, less toxic, and exhibits less depressant action (it does not depress respiration in normal therapy). It is used in the treatment of minor pain and as an antitussive. Codeine is available as a free base or the sulfate or phosphate salt. Thebaine is a convulsant poison rather than a narcotic.

Morphine R = H Codeine R = CH3

Papaverine, a smooth-muscle relaxant that is neither narcotic nor additive, occurs in P. somniferum to the extent of 0.8-1.0%, commonly accompanied by noiscopine (narcotine). Most papaverine used is synthetically produced. The glyoxylate salt is used in treating arterial and venous disorders.

Amaryllidaceae

Amaryllidaceae alkaloids include galanthamine, marge-tine, and narciprimine. Galanthamine is a water-insoluble crystalline alkaloid that exhibits powerful cholinergic activity and analgesic activity comparable to morphine. It has been used to treat diseases of the nervous system. Its derivatives show anticholinesterase, antibacterial, and CNS depressant activity. Narciclasine, margetine, and narciprimine exhibit anticancer activity.

Colchicine

Colchicine, also known as hermodactyl, surinjan, and ephemeron, has some of the most unusual solubility characteristics of any alkaloid: it is soluble in water, alcohol, and chloroform, but only slightly soluble in ether or petroleum ether. Colchicine-type alkaloids are present in ten other genera of the Liliaceae and 19 species of Colchicum. Reviews of the chemistry of colchicine and related com pounds and their history and pharmacology are available. Colchicine has the ability to artificially induce polyploidy or multiple chromosome groups. It is also used to suppress gout.

Cephalotaxus

Cephalotaxus alkaloids are found in the Japanese plum yews, Cephalotoxus spp. The esters, such as harringtonine and homoharringtonine, are potent antileukemic agents. The absolute configuration of the ester moiety has been determined. The a-hydroxy ester is essential for in vivo antileukemic activity.

5 Easy Ways To Stop Smoking

5 Easy Ways To Stop Smoking

Your first day without cigarettes can be difficult, but having a plan will make it easier! Learn what steps to take on the day you quit smoking.

Get My Free Ebook


Post a comment