ALKALOIDS

All are solids except for:

Coniine

Levodopa

Arecoline

Nicotine

Sparteine

Extraction of Alkaloids

Process A:

Process B:

A: acid-treated

B: base-treated

Mayer's reagent

KHgI, cream ppt

Nessler’s Reagent

Alk KHgI, brown ppt

Bouchard's reagent

I2/KI, most sensitive

Dragendorf's reagent

KBiI

Hagner's reagent

Saturated picric acid

Marme's reagent

KCdI

Wagner's reagent

i2/KI, reddish-brown ppt

Valser's reagent

HgI2, red ppt

Sonnencheim's reagent

phosphomolybdic acid

sscheibe's reagent

phosphotungstic acid

Pyridine-Piperidine

Nicotine

Areca

Ipil-ipil

Lobella

Amino acid precursor of Pyridine-Piperidine

Ornithine

Nicotiana tabaccum

Smoking deterrent (Nicorette)

Nicotine

Its tannin content causes oropharengeal cancer

Areca (catechutannin)

CNS stimulant, antihelmintic, taenicide

Areca

Lobelia inflata

Indian tobacco

CNS stimulant, smoking deterrent (Bantron)

Lobella

Leucaena leucocephala

Ascariasis (intestinal infexn by Ascaris lumbricoides)

Ipil-ipil

Tropane Alkaloids

Belladonna

Hyocyamus

Egyptian Hyoscyamus

Duboisia

Stramonium

Withania

Mandragora

Cocaine

Atropine

Scopolamine

Talampunay

Amino acid precursor & plant family of Tropane

Ornithine

Solanaceae

• Atropa belladona

• Deadly Nightshade

• dilation, anticholinergic (dumbbells)

• (-) hyoscyamine → racemized → atropine

belladona

(tropane)

• Hyoscyamus niger leaves

• “henbane"

• hog + bean → toxic to swine (pig)

• 0.04% alkaloid

hyoscyamus

(tropane)

• Hyoscyamus muticus

• “egyptian henbane"

• hyoscyamine + scopolamine

• 1.5% alkaloid

ehyptian hyoscyamus

(tropane)

• Duboisia myoporoides

• commercial source of atropine

duboisa

(tropane)

• Withania somnifera

• commercial source of atropine

withania

(tropane)

• Datura stramonium

• Datura fastuosa = chief source

• “talumpunay", “dimsonweed”, “jamestown weed“

• Scopolamine or hyoscine: Motion sickness

• Hyoscine N-butylbromide: Antispasmodic

• is burned & inhaled for the relief of asthma

stramonium

• Mandragora offcinarum roots

• mandragorine: potent poison, emetic

mandragora

• Huanuco coca - Erythroxylon coca

• Truxillo coca - Erythroxylon truxillense

• Cocaine (methylbenzoylecgonine/benzoylmethylecgonine)
  - crack,coke
  - psychomotor stimulant, euphoria;
  - local anesthetic
  - mg in Brompton’s Cocktail – analgesic for cancer pain
  - Free Basing  inhalation of the vapors of alkaloidal cocaine

cocaine

• Antispasmodic, antisialogogue, mydriatic and cycloplegic

• antidote for cholinesterase inhibitors

• (+) inotropic agent
  

atropine

• tx: motion sickness

• Trans-scop® or Transderm®

scopolamine / hyoscine

• Datura metel L.

• “Thorn Apple”

• yield Scopolamine

talumpunay

amino acid precursor of quinoline alkaloids

tryptophan

quinoline alkaloids

(CC)

Cinchona

Cuprea

• Red cinchona bark – Cinchona succirubra

• Yellow cinchona bark – C. calisaya

• Quinine – antimalarial, toxic water

• Quinidine - antimalarial, antiarrhythmic

• Thalleioquin test = fine blue fluorescence then green ppt

• toxicity: cinchonism = temporary hearing loss
  ringing in the ears (Tinnitus)
  impaired sight

cinchona

• Remijia purdieana, Cupreaceae

• commercial source of quinidine

cuprea

Amino acid precursor of isoquinoline

tyrosine

Isoquinoline alkaloids

Ipecac

Hydrastis

Sanguinaria

Opium

Hydromorphone

Apomorphine

Hydrocodone

Opiates (Morphine, Codene, Noscapine, Papaverine, Thebaine)

• Cephaelis ipecacuanha (br) dried rhizome & root

• Cephaelis acuminate (panama)

• constituent: emetine (amebicide) or methylcephaeline

• use: ipecac syrup –emetic

• Ipecac fluidextract is 14 times more potent

• Ipecac + Opium = Dover’s Powder (diaphoretic

• Paregoric – camphorated opium tincture

• Laudanum – deodorized opium tincture

Ipecac

• methylxanthines

• cannot be precipitated by alkaloidal reagents

• inhibits PDE = inc cAMP

purine alkaloids

purine alkaloids examples

coffee

theophylline

theobromine

cola

guarana

mate

thea

• Cola nitida

• CNS stimulant

Cola

• Coffea arabica, C. robusta, C. liberica

• 1,3,7-trimethylxanthine

• release caffeine from cholinergic acid

• caffeol - aroma of coffee

coffee

test for coffee

amaic acid test - red/brown / transient purple

DOC for a stimulating effect of CNS

coffee

% of decaffeinated coffee

0.08%

effects of PDE inh → inc cAMP

• diuresis

• inc gastric secretion

• inh uterrine contraction

• weak (+) chronotropic & inotropic effects

• 1,3-dimethylxanthine

• Camellia sinensis

• Aminophylline - semi-synth deriv

• Tannic acid test - white heavy ppt

• Use: smooth muscle relaxant → bronchodi (asthma, COPD), tocolytic

Theophylline

• 3,7-dimethylxanthine

• Theobroma cacao seeds

• Diuretic in cardiac & pulmonary edema (preferred over coffee bc of its less stimulating effect in the CNS)

Theobromine

• Paullinia cupana

• Caffeine, catecholamine

• CNS stimulant, astringent

Guarana

• Ilex paraguariensis

• “Paraguay tea“

• caffeine, tannin

• CNS stimulant, astringent

Matē

• Alkaloid class taht do not have N in their heterocyclic ring

• Phenylethylamine deriv

• Tryptophan deriv

Alkaloidal Amine

Alkaloidal amine examples

(PPECK)

Peyote

Psilocybe

Ephedrine

Colchicine

Khat

• Ephedra sinica

• “Ma huang“

• Sympathomimetic: vasocon for HTN, mydriasis, decongestant, bronchodi

Ephedrine

• Colchicum autumnale

• Tx acute gout

• Used in plant genetics bc it can double the chromosomes

Colchicine

• Catha edulis

• “Abyssinian tea“

• cathinone - amphetamine-like effects

Khat

• Lophophora williamsii

• “Mescal buttons”

• shrooms

• mescaline - psychomimetic: hallucinogenic

Peyote

• Psilocybe mexicana

• Psilocybin - psychedelic; hallucinogenic

Psilocybe

Alkaloid class containing the CPPP nucleus

Steroidal Alkaloid

Steroidal Alkaloids examples

Black Hellebore

White Hellebore

Green Hellebore

• Veratrum viride

• "American Hellebore”

• CNS depressant

• hypotensive, insecticide

Green Hellebore

• Veratrum album

• “European Hellebore“

• protoveratrine A&B: toxic deriv

• hypotensive (not used clinically), insecticide

White Hellebore

• Only steroidal alkaloidd that is a CNS stimulant

• (+) inotrope

Black Hellebore

Alkaloid with glyoxaline ring

Imidazole alkaloid

Amino acid precursor of Imidazole

Histidine

• Pilocarpus jaborandi

• Cholinergic agent; miotic

• Tx: glaucoma

• lactone of pilocarpic acid

Pilocarpine

Amino acid pprecursor of Indole Alkaloids

Tryptophan

Indole Alkaloids examples

(PREVNY)

Physostigmine

Rauwolfia

Ergot

Vinca alkaloids

Nux vomica

Yohimbe

• Rauwolfia serpentina

• “Snakeroot”

• Reserpine (Serpasil®): snakebite tx, hypotensive, psychotherapy, sedative, tranquilizing ppt

• S/E: depression, deplete NE storage

Rauwolfia

• Cantharantus rosea

• “ChiChi Rica“ “Madagascar Periwinkle"

• Constituents: Vincristine, Vinblastine (interferes w/ the polymerization of tubulin to microtubules), Vinleurosine, Aniosidine

• Anti-neoplastic

Vinca Alkaloids

Commercial source of Strychnine

Strychnos ignatii (St. Ignatius Bean)

• Strychnos nux vomica

• Constituent: strychnine (toxic CNS stimulant; vermin killer)

• Mandelin's test: violet

• Brucine: alcohol denaturant

• Strychnine poisoning: inh glycine receptors in the spinal cord

• Manifestations: opistothomos, sardonic smile

Nux vomica

• Physostigma venenosum

• “Calabar", “Ordeal Bean“

• Inh. acetylcholinesterase → miosis

• Tx: Glaucoma

• DOC: Atropine toxicity

• Toxicity: Cholinergic crisis (dumbells)

• Antidote: Atropine

Physostigmine / Eserine

Pausinystalia yohimbe

Yohimbe

• Secale cereale

• Parasitic (living) = Claviceps purpurea

• Saphrotic (dead) = Claviceps paspanii

• Constituents: ergonovine (ergometrine & metylsergide – prophylaxis for migraine) – oxytoxic agent, ergotamine
  

Ergot

• Derivative of Ergot

• Was discovered by A. Hoffman is considered as the most active & most specific hallucinogen

• Psychomimetic

• Sympathetic stimulation

Lysergic Acid Diethylamide (LSD)

• Decrease the blood flow into extremities
  > gangrene (St. Anthony’s Fire)

Ergot Alkaloid

• Oxytoxic Agent

• Assist in Labor

Ergonovine / Ergometrine

• Vasorelaxant

• Hypotensive agent

Ergotoxine / Hydergine