Alkaloids 1 • Alkaloids originating from 1-Capsaicinoides (Capsicum annuum [Solanaceae]) Capsaicine:pungent, iritation on the skin, rubafecient in rheumatoid pain 2-Ephedrine, pseudoephedrine (Ephedra sinica) 3-Cathine(Catha edulis)
Ephedrine Ephedra sinica “ma huang”; Used in treatment of common cold, ↑BP and pulse, contraction of blood vessels, bronchodilator, fat combustion Pseudoephedrin vasoconstriction on mucous membranes, rhinitis, Herbal extasy, doping
Ephedra alkaloids
Khat tea: Catha edulis (Celastraceae) Leaves: Flav., vol. oils, cathedulins, tannins, cathinone, cathine,…. Young leaves: cathinone;↓hunger and fatigue, increased alertness, general excitement, ↑self-confidence, talkativeness, “constant mild high” AE: inflammation of oral mucosa, gastric disturbances, anorexia, hypertension, impotence
Alkaloids 2 • Alkaloids originating from -Adrenaline, noradrenaline -Mescaline --Isoquinoline alkaloids ---Benzylisoquinoline alkaloids: Opium alkaloids ---Bis-benzyl-isoquinolinealkaloids:Tubocurarin ---Terpenoidtetrahydro-isoquinoline alkaloids: Ipecac alkaloids (Emetine, cephaeline)
Alkaloids 2 • Alkaloids originating from Adrenaline
Mescalin and Lophophora williamsii (Cactaceae) • Mescal buttons, South American Indians, religious rituals as hallucinogenic [unusual colored hallucinations, flashing lights, euphoria,disturbes normal mental functions. Psychotomimetic]
Alkaloids 3 Alkaloids originating from Colchicine occurs in the seeds and corms; non-basic alkaloid; • Anti-inflammatory; acute attacks of gout; cytotoxic; anti-mitotic • Tox. Symptoms: swallowing difficulties, abdom. pain, ↓BP, muscle cramp, resp. difficulties; Death: resp. arrest, CV collapse • Toxic dose: 10mg; above 40 mg death within 3 days; suicidal attempts
Isoquinoline alkaloids and Benzylisoquinoline alkaloids • Basic structures:
Papaver somniferum (Papaveraceae) • Opium: alkaloid richest drug • Alkaloids: 20-30%, meconic acid: ~5%; lactic acid: 1-2%; other acids, enzyms, proteins, resins, fats • Morphine alkaloids: thebaine, codeine, morphine • Benzylisoquinoline alkaloids: Papaverine • Phthalidisoquinoline alkaloids: Noscapine (narcotine) • Several semisynthetic derivatives: Ethylmorphine, diacetyl morphine (heroine), apomorphine, hydromorphone, hydrocodone, cotarnine,….
Important opium alkaloids Papaverine • Thebaine Codeine Morphine
Opium and morphine • Opium: CNS stimulant, analgesic, hypnotic, narcotic, stimulating / depressing, checks excess peristalsis, pupil contraction; • Crude opium: ~10% morphine (analgesic, sleep inducer, cough treatment) • Powdered/granulated opium: • Laudandum (opium tincture): analgesic, narcotic • Camphorated opium (paregoric): antiperistaltic, diarrhea, dysentery; cough prep. • Dower’s powder (+ ipecac): diophoretic, influenza; sedative ; • Morphine: mental detachment, tolerance, addiction, withdrawal symptoms • CNS: drowsiness, analgesia, euphoria Pupil: miosis Respiration: depressant; respiratory arrest GI: Stomach: HCl↓, small intestine: Biliary and pancreatic juices ↓ (delayed food digestion), large intestine: peristaltic waves↓, tone↑ (spasm, constipation) Bronchi: large doses (bronchconstriction), Nausant and emetic effects, habit formation, …..
Codeine, thebaine, noscapine and papaverine • Codeine (methylmorphine): most widely used opium alkaloid, antitussive and narcotic analgesic in the liver [-CH3]; (1/10 the potency of morphine); less toxic, less habit formation, little euphoria; constipation on long term use • Thebaine: used primarily for the semi-synthetic production of other drugs, incl. codeine; • Papaverine (not morphinane!): Smooth muscle relaxant, spasmolytic, little analgesic effect; male impotence! • Noscapine (not morphinane!): Antitussive and cough suppressant, no analgesic or narcotic action; teratogenic!; antitumor action • Papaveratum is a mixture of opium alkaloid: morhine (85.5%), codeine (7.8%), papaverine (6.7%); pain relief during surgery; may be combined with hyoscine
Semisynthetic and synthetic derivatives of morphine and thebaine 1-Morphine derivatives: codeine, pholcodine, ethylmorphine, hydromorphone, apomorphine, heroine, nalorphine; dextrometorphan, pentazocine, pethidine, fentanyl, methadone, tramadol Morhine antagonist: naloxone 2-Thebaine derivatives: Codeine, etorphine, buprenorphine, oxymorphone :nalbuphine, naloxone, naltrexone
Bis-benzyl-isoquinoline alkaloids: Curare • Dried extract of barks and stems applied to various South American arrow poisons 1-Menispermaceae curare: Chondrodendron tomentosum : Bis-benzyl –THIQ alkaloids; 4-7% alkaloids; d-tubocurarine 2- Loganiaceae curare: Strychnos spp. : Indol alkaloids 3-Mixture of both plants “Monkey test”; “head drop test” d-tubocurarine: H2O-sol., monoquaternary NH4-salt; Paralysis, relaxation of voluntary muscles, competes with acetylcholine at nicotinic receptors; death: muscles of respiration stops to operate; treatment: artificial respiration and specific antidotes: anti-acetylcholine-esterase drugs: Physostigmine, neostigmine Uses: Parkinson’s disease, MS, tetanus; skeletal muscle relaxant, surgery Synth. Analogues: deca-, suxa-methonium; atracurium, vencuronium
Terpenoid tetrahydro-isoquinoline alkaloids Radix ipecacuanha • Cephaelis ipecacuanha, C. acuminata (Fam. Rubiaceae) • Major alkaloids: emetine and cephaeline • Minor alkaloids: psychotrine and O-methyl-psychotrine Ipecac: high doses: emetic; small doses: expectorant Emetine: antiaemebic, anti-protozoan, amebic dysentery, expectorant, antiviral, antitumor; O-methylpsychotrine: AIDS (inhibition of HIV reverse transcriptase) psychotrine O-methyl-psychotrine
