Natural drugs
Drugs that originate in animals, plants, or microorganisms.
Pharmacognosy (生藥學)
An applied science that deals with the biologic, biochemical, and economic features
of natural drugs and their constituents.
Classification of natural drugs
1. Alkaloids (生物鹼): Alkali-like natural compounds
2. Glycosides (配醣體): Compounds that yield one or more sugars among the
products of hydrolysis.
3. Steroids (固醇類): Compounds that contain cyclopentanoperhydrophenantrene
nucleus.
4. Antibiotics (抗生素): A chemical substance that produced by a microorganism
that has the capacity, in low concentration, to inhibit selectively or even to destroy
bacteria and other microorganism through an anti-metabolic mechanism.
5. Volatile oils (精油): Odorous constituents.
Alkaloids (生物鹼)
-Organic nitrogenous compounds with a limited distribution in nature.
-Most possess basic properties and mark physiological activity.
-The nitrogen may exist as a primary amine (RNH2), as a secondary amine (R2NH), as
a tertiary amine (R3N), or as a quaternary amine (R4N+X-).
The names of the alkaloids are obtained in various ways:
1.
2.
3.
4.
5.
From the generic name of the plant yielding them (hydrstine, atropine).
From the specific name of the plant yielding them (cocaine, belladonine).
From the common name of the plant yielding them (ergotamine).
From their physiological activity (emetine, morphine).
From the discoverer (pelletierine).
Extraction and isolation
Function of alkaloids
1. Protection
2. End products of detoxification
3. Regulatory growth factors
Pharmacological action of alkaloid
1. Analgesics and narcotics (morphine)
2. Central stimulants (strychnine)
3. Mydriatics (atropine)
4. Miotics (physostigmine, pilocarpine)
5. Hypertension (ephedrine)
6. Hypotension (reserpine)
Classification of alkaloids based on ring structure or nucleus:
N
N
H
piperridine
N
N
quinoline
pyridine
isoquinoline
N
N
N
H
N
H
tropane
indole
H
N
N
N
N
purine
imidazole
Classification of alkaloids based on biosynthetic precursor:
COOH
COOH
COOH
NH2
phenylalanine
H
NH2
ornithine
N
H
tryptophan
tyrosine
COOH
H2N
NH2
NH2
HO
COOH
COOH
H2N
NH2
H
lysine
N
NH
NH2
histidine
Tropane Alkaliods
N
tropane
Belladonna leaf (Deadly nightshade leaf) (顛茄葉)
-Consists of the dried and flowering top of Atropa belladonna (Solanaceae 茄科)
-Atropa: Greek Fate who cuts the thread of life.
-Belladonna: from Italian bella, meaning beautiful, and donna, meaning lady. (The
juice of the berry, when placed on eyes, causes dilation of the pupil thus giving a
striking appearance.)
-3/4 of the alkaloid mixture is (-)-hyoscyamine; 1/4 is atropine, which is formed by
racemization during extraction.
-Uses: parasympathetic depressant (spasmolytic agent); used as adjunctive therapy in
the treatment of peptic ulcer; functional digestive disorders, including spastic mucous
and ulcerative colitis; diarrhea; pancreatitis; control excess motor activity of urinary
tract.
Hyoscyamus leaf (莨菪葉)
-dried leaf and flowering and fruiting top of Hyoscyamus niger (Solanaceae).
-contains 3/4 of hyoscyamine and 1/4 of scopolamine.
-Uses: parasympathetic.
Stramonium leaf (曼陀羅葉)
-dried leaf and flowering and fruiting top of Datura strmonium (Solanaceae).
-contains principly hyoscyamine with small portion of scopolamine and trace of
atropine.
-Uses: anticholinergic.
Hyoscyamine
N
CH3
H
CH2OH
O
H
O
-usually obtained from species of Hyoscyamus or other genera of Solanaceae.
-readily hydrolyzed by boiling in dilute acids or alkalies to form tropine and tropic
acid.
N
CH3
H
O
N
CH3
CH2OH
HO
CH2OH
H
O
-Uses: anticholinergic.
H
OH
+
H
O
Scopolamine
N
CH3
O
H
CH2OH
O
H
O
Anticholinergic; central nervous system depressant used for preanesthetic sedation
and for obstetric amnesia in conjunction with analgesics; prevention of nausea and
vomiting associated with motion sickness.
Cocaine
N
CH3 O
O
CH3
N
CH3 O
O
OH
O
H
H
O
cocaine
ecgonine
CH3
+
HO
O
benzoic acid
-obtained from the leaves of Erytroxylum coca and its variety or prepared by
semisynthesis from plant-derived ecgonine.
- Erytroxylum: from Greek, meaning red wood (color of the plant).
- coca: Spanish name for tree.
-cultivated in Bolivia, Colmbia, and Peru; each produces about 50,000 metric tons of
leaves a year.
-uses: local anesthetic.
-other physiological effect: (1) powerful central nervous system stimulant with a
strong abuse potential; (2) euphoric excitement is rapidly produced when cocaine is
sniffed.
-acute toxicity from excess dose: (1) extreme agitation, restless, confusion, blurred
version, and tremors; (2) induces paranoid thinking, hallucinations, cardiac
arrhythmia, acute myocardial infartion.
Quinoline alkaloids
N
Cinchona bark (Peruvian bark)
-dried bark of the stem and the root of Cinchona succirubra or its hybrids, or other
species of Cinchona and heir hybrids.
- Cinchona: named in honor of the countess of Chinchon.
- succirubra: means juice.
-indigenous to the Andes of Ecuador and Peru.
-grow at an elevation of 1000 to 3000 meters, cultivated in Indonesia and India.
-trees that are 6-9 years ild possess the maximum amount of alkaloids.
-contained some 25 closely related alkaloids, the most important of which are quinine,
quinidine, cinchinine, and cinchonidine.
-uses: treatment of malaria fever.
Quinine
H
H
H
MeO
HO
H
N
N
-obtained from bark of Cinchona species.
-use: antimalarial
-mechanism: intercalation of the quinoline moiety into the DNA of the plasmodium
parasite.
Quinidine
H
H
HO
H
MeO
H
N
N
-obtained from bark of Cinchona species.
-a stereoisomer of quinine.
-use: treatment of cardiac arrhythmias.
Isoquinoline alkaloids
N
Ipecac (吐根)
-consists of dried rhizome and roots of Cepaelis ipecacuanha (Brazilian ipecac) or
Cepaelis acuminata (Nicaragua or Panama ipecac).
-contains emetine.
-uses: treatment of drug overdose and in certain poisonings (syrup), produces emesis
through a local irritant effect on the gastrointestinal mucosa and a central medullary
effect by stimulation of the chemoreceptor trigger zone.
Emetine (吐根鹼)
MeO
N
MeO
H
C2H5
H
OMe
HN
OMe
-uses: antiamebic by inhibiting polypeptide chain elongation; possesses expectorant
and emetic properties.
Curare or South American arrow poison
-Crude dried extract from the bark and stem of Strychnos castelnaei.
-Curare: Indian word for poison.
-Crude extract exhibits a paralyzing effect on voluntary muscle by blocking nerve
impulses to skeletal muscles at myoneural junction.
-Tubocurarine is the most important constituents.
MeO
Me
N
+ Me
HO
O
HO
-a bisbenzylisoquinoline quaternary aklaloids.
-a skletal muscle relaxant to secure muscle
relaxation in surgical procedures without deep
anesthesia.
O
NMe
OMe
tubocurarine
Opium (鴉片)
-air-dried milky exudates obtained by incising the unripe capsules of Papaver
somniferum (Papaveraceae) (罌粟科).
-opium: Greek, meaning poppy juice.
-Papaver: Latin, means poppy.
-somniferum: Latin, means to produced sleep.
-an annual herb with large, showy, solitary flowers that vary in color from white to
pink or purple.
-first cultivated in Mediterranean region, then introduced into India by Alexander the
Great.
-cutivation is controlled internationally by the International Narcotics Control Board
of the United Nations.
-contain morphine, codeine, noscapine, papaverine, and thebaine.
-uses: anageic hypnotic, narcotic,
Morphine
N CH3
H
1
6
3
HO
OH
O
-the most important opium alkaloid.
-contains a phenolic and an alcoholic hydroxyl group.
-used as narcotic analgesics; strongly hypnotic and narcotic; induced nausea, vomiting,
constipation, and habit formation.
Heroine (Diacetylmorphine)
N CH3
H
OAc
O
OAc
-formed by acetylation of morphine.
More potent than morphine.
Hydromorphine
N CH3
H
6
HO
O
O
-6-OH replaced by a ketone.
-more potent than morphine.
-less nausea and constipation.
Codeine
N CH3
H
6
MeO
OH
O
-obtained from opium or prepared by morphine methylation.
-anticough
Hydrocodone
N CH3
H
6
MeO
O
O
-anticough and antitissue.
Synthetic analgesic nacortics
Me
O
Me
N Me
Me
N
Me
COOC2H5
Methadone
Meperidine
Features possessed by central acting analgesics
(1) a central quaternary carbon.
(2) a tertiary nitrogen.
(3) a phenyl group or isostere attached to central carbon.
(4) a two carbon bridge separating the central carbon and the tertiary nitrogen.
Paspaverine
MeO
NH
MeO
OMe
OMe
-occurs in opium
-smooth muscle relaxant.
Tolerance and enkephalin receptor
Enkephalins
Tyr-Gly-Gly-Phe-Met
Tyr-Gly-Gly-Phe-Leu
Endophines
Antidote of morphine: Naloxone
Abstinence of morphine
8-12 hr: lacrimation, rhinorrhea, yawning, diaphoresis, restless sleep
20 hr: gooseflesh, dilated pupil, agitation, tremors,
2-3 days: weakness, insomnia, chills, intestine cramps, nausea, vomiting, diarrhea,
violent yawning, muscle aches in the legs, severe low back pain, elevation of blood
pressure, diaphoresis, wave of gooseflesh.
Indole alkaloids
N
H
Rauwolfia Serpentina (印度蛇根)
-dried root of Rauvolfia serpentina (Apocynaceae)(夾竹桃科)
-Rauvolfia: in honor of Dr. Leonhard Rauwoff, a noted 16th century German botanist,
physician, and explorer.
-Serpentina: refers to the long, tapering, snakelike roots of the plant.
-used by the medicine men of India to treat snakebite and insanity for centuries.
-contain reserpine, resinanamine, and δ-yohimbine.
-excert hypotensive effect by depletion of norepinephrine through inhibition of
catecholamine storage in postganglionic adrenergic endings.
Reserpine
H
N
N
H
MeO
O
O
OMe
OMe
OMe
H
H
H3COOC
OMe
-chief alkaloid from Rauvolfia serpenina.
-uses: antihypertensive and tranquilizer.
Rescinnamine
H
N
N
H
MeO
O
OMe
O
H
H
H3COOC
OMe
OMe
OMe
-occurs in several speies of Rauvolfia.
-uses: antihypertensive.
Deserpine (11-desmethoxyreserpine)
N
11
N
H
H
H
H3COOC
H
O
O
OMe
OMe
OMe
OMe
-obtained from Rauvolfia canescens.
-uses: antihypertensive and tranquilizer.
Catharanthus (periwinkle)(長春花)(日日春)
-dried whole plat of Catharanthus roseus (Apocynaceae)
-originated in Madagascar.
-folkore used as hypoglycemic agent.
-peripheral granulocytopenia and bone marrow depression in rats was observed by
Canadian group of Noble, Beer, and Cutts.
-continued study led to the isolation of vinblastine, which produced severe leukopenia
in rats.
-more than 70 different alkaloids have isolated from Catharanthus.
Vinblastine
OH
N
CH2CH3
COOCH3
N
N
H
CH2CH3
OCOCH3
MeO
COOCH3
H OH
N
Me
-the salt of an alkaloid extracted from Catharanthus.
-uses: treatment of Hodgkin’s disease, lymphocytic lymphoma, advanced testicular
carcinoma, and breast cancer.
Vincristine
OH
N
CH2CH3
COOCH3
N
N
H
CH2CH3
OCOCH3
MeO
COOCH3
N
H OH
CHO
-obtained from Catharanthus.
-no cross-resistance has been observed between vincristine and vinblastine.
-uses: treatment of acute leukemia, Hodgkin’s disease, lymphosarcoma, and
neuroblastoma.
Nux Vomica (馬錢子)
-dried, ripe seed of Strychnos nux-vomica (Loganiaceae)
-Strychnos: Greek name for poisonous plant.
-nux-vomica: from two Latin words and means a nut that xauses vomiting.
-a tree about 12 meters tall; native to East Indies.
-Fruit is berry with 3-5 seeds.
-contained strychnine and brucine (dimethoxystrychnine)
-uses: commercial sources for strychnine and brucine.
Strychnine
N
H
H
N
H
O
H
O
-obtained from nux vomica.
-produces excitation of all parts of the central nervous system and block inhibitory
spinal impulses at the postsynaptic level; leads to an exaggeration in reflexes with
resulting tonic convulsion.
Physostigma (毒扁豆)
-dried, ripe seed of Physostigma venenosum (Leguminosae)
-Physostigma: Latin, means an inflated or bladderlike stigma.
-venenosum: Latin, means full of poison.
-a perennial woody climber native to West Africa.
-contains physostigmine, eseramine, etc.
Physostigmine
CH3
N H
HNCOO
CH3
N
H
CH3
-obtained from Physostigma venenosum.
-uses: reversible inhibition of cholinesterase; miosis (contraction of ciliary muscle);
decrease in intraocular pressure.
Ergot (麥角)
-dried sclerotium of Claviceps purpurea developed on the plants of rye, Secale
cerreale (Gramineae).
- Claviceps: clublike character of the sclerotium.
-purpurea: refers to its purpur color.
-At present, ergot alkaloids are obtained on a commercial scale from both parasitic
and saprophytic sources.
-contains errgonovine, ergotamine, and ergotoxine.
-The medicinally useful alkaloids, either natural or semisynthetic, are all derivative od
(+)-lysergic acid.
-uses: sources of ergot alkaloids; oxytocic.
Ergonovine
O
R
N
CH3
H
H
CH3
R = NH
CH2OH
N
H
-soluble in water.
-Oxytocic effect is noted within 5 minutes (orally, subcutaneously, or
intramuscularly).
-Vasoconstrictor action is much less marked.
-increase the frequency and amplitude of uterine contractions; decrease blood loss
from postpartum uterus.
Ergotamine
O
R
N
CH3
R=
H
H3C
OH
O
N
H
N
N
O
O
N
H
-a specific anagesic in treatment of migraine.
-reduced extracranial blood flow and decreases the amplitude of pulsation in the
cranial arteries.
Lysergic acid diethylamide (LSD)
O
R
N
CH3
H
R = N(C2H5)2
N
H
-dose not occur in nature.
-producev a predominant central sympathetic stimulation that parallels a slight
depression.
-the most active and most specific psychotomimetic agent known.
Imidazole alkaloids
H
N
N
Pilocarpus (毛果芸香葉)
-consists of the leaflet of Pilocarpus jaborandi.
-Shrubs indigenous ton Brazil.
-contains pilocarpine.
Pilocarpine
C2H5
H
N
O
N
-obtained from Pilocarpus jaborandi Pilocarpus jaborandi.
-stimulates the muscarinic receptors in the eye, causing constriction of the pupil and
contraction of the ciliary muscle.
-uses: treatment of glaucoma.
Alkaloid amines
Ephedra (ma huang)
-entire plant or the overground portion of Ephedra sinica (Gnetaceae)
-ma: means astringent; huang: means yellow.
-used as a medicine in China for more than 5000 years.
Ephedrine
OH NHCH3
CH3
H H
-obtained from Ephedra spp. or by reductive condensation between
L-1-phenyl-1-acetylcarbinol and methylamine.
H3C
Acetyl-CoA
CHO
O
OH NHCH3
CH3CN
HO
CH3
H H
H
-uses: potent sympathomimetic that stimulates α, β1, and β2 adrenergic receptors;
causes vasoconstriction and cardiac stimulation; produced a rather lasting rise in
blood pressure.
Colchicine (秋水仙素)
MeO
NHCOCH3
MeO
OMe
O
OMe
-obtained from Colchicum autumnale (Liliaceae) or other species of Colchicum.
-inhibit leukocyte migration and reduceds lactic acid production by leukocytes which
results in a decreased deposition of uric acid.
-reduction in phagocytosis which decreases inflammatory response.
-uses: treatment of gout; doubling of chromosomes in plant genetics.
Purine bases
O
H
N
N
N
purine
Me
N
O
O
Me
Me
N
N
N
Me
caffeine
N
O
N
O
H
N
N
Me
theophylline
N
HN
N
O
Me
N
N
Me
theobromine
Caffeine
-occurs in coffee (Coffea arabica), tea (Thea sinensis), cacao (Theobroma cacao), and
kola (Cola nitida).
-CNS stimulant.
Theophylline
-occurs in tea.
-uses: smooth muscle relaxants for the symptomatic relief or prevention of bronchial
asthma; diuretic.
Theobromine
-obtained from te dried seed of cacao.
-little CNS stimuation.
-uses: diuretic and smooth muscle relaxant.