Alkaloids Part 2 - Pharmacognosy Notes

Classes of Alkaloids

  • Isoquinoline alkaloids

    • Ipecac (emetine, cephaline, psychotrine)

    • Hydrastis or goldenseal

    • Sanguinarine

    • Curare

    • Opium Alkaloids (Morphine, Codeine, Heroin, Papaverine, Hydromorphone)

  • Indole alkaloids

    • Rauwolfia serpentina, Vincristine, Ergonovine, LSD

      • Reserpine, Yohimbine

      • Catharanthus alkaloids: Vindesine, Vinorelbine

      • Nux vomica (Brucine, Strychnine)

      • Ergot (Ergotamine)

  • Ergot alkaloids

  • Imidazole alkaloids

  • Steroidal alkaloids

  • Alkaloidal amines

  • Quinolizidine alkaloids

  • Purine bases

Isoquinoline Alkaloids

  • Majority have the isoquinoline ring structure.

  • Derived from benzylisoquinoline intermediates.

  • Result from condensation of phenylethylamine with phenylacetaldehyde derivatives.

  • Both moieties derived from phenylalanine or tyrosine.

  • Norlaudanosoline is a key intermediate.

  • Demethylation of codeine leads to morphine.

IPECAC

  • From dried rhizome and roots of Cephaelis ipecacuanha or Cephaelis acuminata (Fam. Rubiaceae).

  • Principal alkaloids: Emetine, Cephaeline and Psychotrine

  • Use: Treatment of drug overdose and poisonings.

  • Dose: 15 ml followed by 1-2 glasses of water, repeat once in 20 minutes if no emesis.

  • Ipecac syrup is weaker than ipecac fluidextract.

  • Ipecac with opium (Dover's powder) acts as a diaphoretic.

Emetine

  • From ipecac or synthetic methylation of cephaeline.

  • Anti-amoebic agent.

  • Emetine hydrochloride is administered IM or SQ (1 mg/kg, not exceeding 65 mg daily for max 5 days).

Emetine Hydrochloride

  • Not given orally due to expectorant and emetic properties.

Hydrastis or Goldenseal

  • From dried rhizome and roots of Hydrastis canadensis (Fam. Ranunculaceae).

  • Principal alkaloids: Hydrastine, Berberine and Canadine.

  • Use: Astringents in inflammation of mucous membranes.

Hydrastine

  • Soluble in chloroform, alcohol, and ether; insoluble in water.

Berberine

  • Soluble in water; insoluble in ether.

Sanguinaria or Bloodroot

  • From dried rhizome of Sanguinaria canadensis (Fam. Papaveraceae).

  • Contains protopine series alkaloids: sanguinarine, chelerythrine, protopine, allocryptopine.

  • Use: Stimulating expectorant and emetic.

  • Dose: 125 mg.

Curare or South American Arrow Poison

  • Dried extract from bark/stems of Strychnos spp. (Loganiaceae) and Chondodendron tomentosum (Menispermaceae).

  • Contains (+)-Tubocurarine.

  • Exhibits paralyzing effect on voluntary muscle.

  • Blocks nerve impulses to skeletal muscles at the myoneural junction.

  • The "head-drop" test describes the least amount of Tubocurarine to produce muscle relaxation

  • Uses: Muscle relaxant in surgery, control convulsions, diagnostic aid in myasthenia gravis.

  • Dose: Initial dose: 200 to 400 mg per kg of body weight, not exceeding 27 mg, then 40 to 200 mg per kg, repeated as necessary.

Opium or Gum Opium

  • Air-dried milky exudate from unripe capsules of Papaver somniferum (Fam. Papaveraceae).

  • Morphine was first isolated from opium in 1806.

  • Indian opium is a licit source, yielding about 10% anhydrous morphine.

  • Contains >30 alkaloids, including:

    • Morphine (4-21%)

    • Codeine (0.8-25%)

    • Noscapine (4-8%)

    • Papaverine (0.5-2.5%)

    • Thebaine (0.5-2%)

  • Acts on the CNS as analgesic, hypnotic, and narcotic.

  • Checks excessive peristalsis and contracts the pupil.

  • Paregoric (camphorated opium tincture) is an anti-peristaltic agent.

  • Laudanum (opium tincture) is used similarly to paregoric.

Poppy Seed or Maw Seed

  • Dried seed of Papaver somniferum var. nigrum.

  • Used in baking; contains about 50% fixed oil (poppy seed oil).

  • Contains no significant amount of alkaloids.

Alkaloids of Opium

Morphine

  • Prototype opiate analgesic.

  • Acts at CNS sites to produce analgesia.

  • μ receptor agonist: analgesia, euphoria, respiratory depression, physical dependence.

  • κ receptor agonist: analgesia, miosis, sedation.

Codeine

  • Most widely used opium alkaloid.

  • Obtained from opium or prepared from morphine by methylation.

  • Narcotic analgesic and antitussive; used as sedative.

Diacetylmorphine or Heroin

  • Formed by acetylation of morphine.

  • More potent than morphine.

Papaverine

  • Occurs naturally in opium (1%) or produced synthetically.

  • Smooth muscle relaxant used for cerebral and peripheral ischemia.

Hydromorphone

  • Ketone group replaces hydroxyl group; adjacent double bond removed.

  • Powerful narcotic analgesic with strong respiratory depression.

Hydrocodone Bitartrate

  • Ketone group replaces hydroxyl group; adjacent double bond saturated.

  • Antitussive.

Indole Alkaloids

Rauwolfia Serpentina

  • Dried root of Rauwolfia serpentina (Fam. Apocynaceae).

  • Contains reserpine-rescinnamine group of alkaloids (0.15-0.20% as reserpine).

  • Exerts hypotensive effects by depleting catecholamine and serotonin stores.

  • Sedative and tranquilizing properties related to amine depletion in the CNS.

Reserpine

  • Antihypertensive and antipsychotic agent.

Rescinnamine

  • Used to treat mild essential hypertension.

Deserpidine

  • Same uses as Rauwolfia serpentina and reserpine; fewer side effects.

Yohimbine

  • From bark of Pausinystalia yohimbe (Fam. Rubiaceae).

  • Treats impotence in patients with vascular or diabetic problems.

Catharanthus or Vinca

  • Dried whole plant of Catharanthus roseus (Fam. Apocynaceae).

  • Contains bisindole compounds with oncolytic activity: vinblastine, vinleurosine, vinrosidine, and vincristine.

Vinblastine Sulfate

  • Treats Hodgkin’s disease, lymphocytic anemia, histiocytic lymphoma, advanced testicular carcinoma, Kaposi’s sarcoma and breast cancer.

Vincristine Sulfate

  • Treats acute lymphocytic leukemia, Hodgkin’s disease, lymphosarcoma, neuroblastoma and Wilm’s tumor.

Vindesine

  • Semisynthetic derivative of vinblastine.

  • Activity resembles vincristine.

Vinorelbine Tartrate

  • Treats non-small cell lung cancer.

Nux vomica

  • Dried ripe seed of Strychnos nux vomica (Fam. Loganiaceae)

  • Chief alkaloids: Strychnine and brucine.

Strychnine

  • Extremely toxic; central stimulant.

Brucine

  • Less toxic than strychnine; used as alcohol denaturant.

Physostigma, Calabar Bean

  • Dried ripe seed of Physostigma venenosum (Fam. Fabaceae).

  • Contains physostigmine (eserine), eseramine, geneserine, and physovenine.

Physostigmine

  • Reversible inhibitor of cholinesterases.

  • Employed in ophthalmology to treat glaucoma.

Ergot

  • Sclerotium of Claviceps purpurea (Fam. Clavicipitaceae) on rye.

Ergonovine Maleate

  • Oxytocic effect.

Methylergonovine Maleate

  • Semisynthetic homolog of ergonovine; oxytocic.

Ergotamine Tartrate

  • Used to prevent or abort vascular headaches, including migraine and cluster headaches.

Methysergide Maleate

  • Serotonin antagonist used for prophylaxis of vascular headache.

Lysergic Acid Diethylamide or LSD

  • Semisynthetic; potent psychotomimetic agent.

Imidazole Alkaloids

Pilocarpine

  • From leaflets of Pilocarpus jaborandi (Fam. Rutaceae).

  • Stimulates muscarinic receptors.

Steroidal Alkaloids

Veratrum Viride

  • Rhizome and roots of Veratrum viride (Fam. Liliaceae).

  • Possesses hypotensive, cardiac depressant and sedative properties.

Alkaloidal Amines

  • Nitrogenous portion (amine) is not part of a cyclic ring.

Ephedra or Ma Huang

  • From Ephedra sinica (Fam. Gnetaceae).

  • Chief alkaloid: Ephedrine

Colchicine

  • From Colchicum autumnale (Fam. Liliaceae).

  • Used for gout.

Purine Alkaloids

  • Methylated derivatives of 2,6-dioxypurine (xanthine).

  • Natural Methylxanthines: Caffeine, Theophylline, Theobromine.

Caffeine

  • Occurs in coffee, tea, cacao, guarana, kola and mate.

Theophylline

  • Prepared leaves and leaf buds of Camellia sinensis (Fam. Theaceae).

  • Smooth muscle relaxant, antiasthma and diuretic.

Theobromine

  • From dried seed of Theobroma cacao (Fam. Sterculiaceae).

  • Diuretic and smooth muscle relaxant.