[9.2] ALKALOIDS

• cinchona

• cuprea bark

• dita

• happy tree

QUINOLINE ALKALOIDS

• EXAMPLES

peruvian bark

CINCHONA / CINCHONA BARK

• other name

• Cinchona succirubra (Red cinchona) 

• C. calisaya (Yellow cinchona, Calisaya bark)

CINCHONA / CINCHONA BARK / PERUVIAN BARK

• source

• Quinine (antimalarial); prevents conversion of heme (toxic) to hemozoin (nontoxic) = death of plasmodium 

• Quinidine (antiarrhythmic); for prophylaxis of cardiac arrhythmias & treatment of A-fib

CINCHONA / CINCHONA BARK / PERUVIAN BARK

• constituents

• Overdose: “cinchonism”- loss of hearing, ringing in the ears, impaired sight 

• Quinine and quinidine is identified by Thalleoquine reaction (+) emerald green

CINCHONA / CINCHONA BARK / PERUVIAN BARK

• notes

Remijia purdieana

CUPREA BARK

• source

Commercial source of quinidine

CUPREA BARK

• constituents

Alstonia scholaris

DITA / AUSTRALIAN QUININE BARK

• source

Ditamine

DITA / AUSTRALIAN QUININE BARK

• constituents

Antimalarial

DITA / AUSTRALIAN QUININE BARK

• notes

Camptotheca acuminata

HAPPY TREE

• source

Camptothecin

HAPPY TREE

• constituents

• Acts as topoisomerase inhibitors especially in malignant cells

• Camptothecin derivatives (ex. irinotecan, topotecan) are used for treatment of several types of cancer such as colon and lung cancer

HAPPY TREE

• use

• ipecac

• goldenseal

• blood root

• tubocurarine

• opium

ISOQUINOLINE ALKALOIDS

• examples

• Rhizome and root of: 

  • Cephaelis ipecacuanha (Rio/Brazilian) 

  • Cephaelis acuminate (Nicaragua, Panama, Cartagena Ipecac) )

IPECAC

• source

• Emetine 

• Cephaline 

• Psychotrine

IPECAC

• constituents

• local emetic (irritant in GI)

• in poison antidote kits

IPECAC

• use

• dver’s powder

• emetine HCl

IPECAC

• related drugs

Dover’s powder

- 10% opium + ipecac (diaphoretic)

Emetine HCl

- antiprotozoan, antiamebic (IM, SC)

MOA: block protein synthesis

Hydrastis canadensis

GOLDENSEAL / HYDRASTIS

• source

• Hydrastine

• Berberine

• Canadine

GOLDENSEAL / HYDRASTIS

• constituents

Astringent in inflammation of mucous membranes

GOLDENSEAL / HYDRASTIS

• use

Sanguinaria canadensis

BLOOD ROOT / SANGUINARIA

• source

Papaveraceae

BLOOD ROOT / SANGUINARIA

• family

• Sanguinarine

• Chelerythrine

• Protopine

BLOOD ROOT / SANGUINARIA

• constituents

• used by Indians to stain faces

• Emetic

• Stimulant

BLOOD ROOT / SANGUINARIA

• use

Strychnos castelnaei

SOUTH AMERICAN ARROW POISON / TUBOCURARINE / CURARE

• source

Loganiaceae

SOUTH AMERICAN ARROW POISON / TUBOCURARINE / CURARE

• loganiaceae

Tubocurarine

SOUTH AMERICAN ARROW POISON / TUBOCURARINE / CURARE

• constituents

• Nondepolarizing skeletal muscle relaxant without deep anesthesia 

  • MOA: block nerve impulses to skeletal muscles → paralyzing effect 

• Head drop test in rabbits: least amount of drug capable of producing relaxation

SOUTH AMERICAN ARROW POISON / TUBOCURARINE / CURARE

• use

• milky exudate (unripe capsule) of Papaver somniferum 

• “Stone of Immortality”

OPIUM / GUM OPIUM

• sources

morphine

OPIUM / GUM OPIUM

• constituents

• CNS stimulant then depressant

• Narcotic analgesic

• Hypnotic 

OPIUM / GUM OPIUM

• use

Prepared Opium BP/EP:

contains 10% morphine & minimum 1% codeine; thebaine limited to 3%

• Paregoric / Camphorated opium tincture

• Laudanum / Opium tincture / Deodorized opium tincture

• poppy seed

OPIUM / GUM OPIUM

• related drugs

Indian opium:

only elicit source of Opium; Contains morphine, codeine, noscapine, papaverine, thebaine

• morphine

• codeine

• heroin

• apomorphine

• papaverine

• hydromorphone

• hydrocodone

• noscapine/narcotine

• diphenxylate, loperamide

• meperidine, fentanyl

opium alkaloids

Morphine

• most important opium alkaloid 

Narcotic analgesic, hypnotic

Morphine

• use

nausea and vomiting, constipation

Morphine

• ae

Antitussive, sedative, narcotic analgesic  

Codeine / methylmorphine

• use

Codeine / methylmorphine

most widely used

Heroin / diacetylmorphine

• habit-forming 

• More pronounced effects than morphine

Apomorphine / dehydrated morphine

central emetic for poisonings

Papaverine

• smooth muscle relaxant

• antitussive

Hydromorphone

• powerful narcotic analgesic

• strong respiratory depressant

Hydrocodone

antitussive

Noscapine / narcotine

Antitussive; no narcotic properties (“anarcotine”)

Diphenoxylate, Loperamide

Antidiarrheal

Meperidine, Fentanyl 

Anesthetic

Meconic acid

- detected by formation of deep red color on addition of ferric chloride

• Long been used to indicate opium

• Chemotaxonomic marker for Papaveraceae

narcotine and narceine (opium), canadine, berberine and hydrastine (Hydrastis), and sinomenine (Sinomenium)

(+)-Reticuline gives rise to

phenolic nature

•  Solubility of morphine in NaOH is explained by its

sodium hydroxide

Codeine is precipitated by

INDOLE ALKALOIDS

• Derived from tryptophan

• Some indoles are embedded in a larger ring system (ex. ergotamine)

• A unique case for physostigmine- though it is an indole alkaloid by convention (blue circle), in pharmacology context it is always classified as a carbamate (green circle

hallucinogenic (ex. amanitins, reserpine, strychnine, Mitragyna alkaloids)

Indole derivatives can sometimes be _

• rauwolfia

• periwinkle

• nux vomica

• ignatia

• physostigma

• ergot

INDOLE ALKALOIDS

• examples

RAUWOLFIA / INDIAN SNAKEROOT

• other name

root of Rauvolfia serpentina

RAUWOLFIA / INDIAN SNAKEROOT

• source

apocynaceae

RAUWOLFIA / INDIAN SNAKEROOT

• family

Reserpine

RAUWOLFIA / INDIAN SNAKEROOT

• constituents

• Hypotensive, 

• Sedative  

• Tranquilizer 

• psychotherapeutic effect 

MOA: depletion of NE by inhibiting storage in postganglionic adrenergic endings

RAUWOLFIA / INDIAN SNAKEROOT

• use

Catharanthus roseus

 PERIWINKLE / CHICHIRICA / VINCA / CATHARANTUS

• source

• Vincristine

• Vinblastine

 PERIWINKLE / CHICHIRICA / VINCA / CATHARANTUS

• constituents

• Antineoplastic

• Oncolytic 

 PERIWINKLE / CHICHIRICA / VINCA / CATHARANTUS

• use

• arrest cell division at metaphase, antimitotic

Periwinkle

• MOA:

Strychnos ignatii

IGNATIA / ST. IGNATIUS BEAN 

• source

Commercial source of strychnine (vermin killer) and brucine

IGNATIA / ST. IGNATIUS BEAN 

• use

Physostigma venenosum

 PHYSOSTIGMA / CALABAR BEAN / ORDEAL BEAN 

• source

Physostigmine (aka eserine)

 PHYSOSTIGMA / CALABAR BEAN / ORDEAL BEAN 

• constituents

• For treatment of glaucoma and myasthenia gravis (MG) 

• Antidote to anticholinergic poisoning 

 PHYSOSTIGMA / CALABAR BEAN / ORDEAL BEAN 

• use

Anticholinesterase (reversible cholinesterase inhibitor), enhances effect of acetylcholine

physostigma moa

MOA:

Dried sclerotium of fungus Claviceps purpurea developed on rye bread Secale cereale (parasitic method)

ERGOT / RYE ERGOT / SECALE CORNUTUM / SPURRED RYE 

• source

Derivative of lysergic acid

ERGOT / RYE ERGOT / SECALE CORNUTUM / SPURRED RYE 

“St. Anthony’s Fire”; due to vasoconstrictive effects

ERGOT / RYE ERGOT / SECALE CORNUTUM / SPURRED RYE 

• gangrenous ergotism

•  associated with vitamin A deficiency 

ERGOT / RYE ERGOT / SECALE CORNUTUM / SPURRED RYE 

• convulsive ergotism

• Oxytocic

• Uterine stimulant

Ergonovine / ergometrine

oxytocic (Methergine) 

Methylergonovine

oxytocic, but used as specific analgesic for migraine

Ergotamine

•  ↓intracranial BP, ↓ amplitude of pulsation in cranial arteries 

• +caffeine → cerebral vasoconstriction 

Ergotamine

• moa

for migraine

Dihydroergotamine

• water insoluble mixture of ergocristine, ergocornine, and ergocryptine 

  • Vasorelaxation, ↑cerebral blood flow, ↓ systemic BP, bradycardia 

  • Hydergine

Ergotoxine

Nucleus from tryptophan & mevalonate

Ergoline

• serotonin antagonist

• prophylaxis for migraine

Methysergide maleate

• most active and specific psychotomimetic

  • Discovered by A. Hoffman 

  • Hallucinogenic, psychomimetic,

Lysergic acid diethylamide (LSD)

• Rivea corymbosa and other Ipomoea spp.) 

• Hallucinogenic, has lysergic acid amide (ergine)

Ololiuqui

pilocarpus jaborandi

IMIDAZOLE ALKALOIDS

Leaflets of Pilocarpus jaborandi

 PILOCARPUS JABORANDI

• source

Rutaceae

 PILOCARPUS JABORANDI

• family

Pilocarpine

 PILOCARPUS JABORANDI

• constituents

muscarinic agonist → treatment of glaucoma (similar to physostigmine)

 PILOCARPUS JABORANDI

• use

• Solanum alkaloids

• Veratrum alkaloids

STEROIDAL ALKALOIDS

• Classification by number of carbons: C21

• Apocynaceae 

• Buxaceae

STEROIDAL ALKALOIDS

• Classification by number of carbons: C27

• Jervine

• Pseudojervine

• Veratrosine

STEROIDAL ALKALOIDS

• Classification by abundance of oxygen: Jerveratrum

• Germine 

• Protoverine 

• Veracevine

STEROIDAL ALKALOIDS

• cerveratrum

• green/ american hellebore

• white/european hellebore

steroidal alkaloids examples

Veratrum viride

Green / American Hellebore

• source

Germidine and germitrine

Green / American Hellebore

• constituents

• Hypotensive 

• Cardiac depressant 

• Sedative 

• Used as insecticide

Green / American Hellebore

• use