Alkaloids

Question 1

What are Alkaloids?

Answer 1

Chemical classification of alkaloids
* Heterocyclic alkaloids are ‘true’ alkaloids (nitrogen - alkaline- in heterocyclic ring).
* Non-heterocyclic ‘alkaloids’ are protoalkaloids, or amines e.g. ephedrine: contains a nitrogen atom, but nitrogen is not in any part of any ring system.
* Pseudo-alkaloid: not derived from amino acid but nitrogen is in heterocyclic ring, e.g. caffeine

Godo to extract in tincture and are very bitter.

Question 2

What effect do they have on the body?

Answer 2

Able to cross the blood brain barrier so have profound actions especially their effect on central nervous system. Usually:
* Depressant or stimulant, as able to interact with various neurotransmitter receptors.
* Morphine and codeine, CNS depressant and analgesic/narcotic.
* Caffeine, cocaine are CNS stimulants.
* Hyoscamine is a parasympathetic depressant.
* Atropine, a mydriatic.
* Pilocarpine, a miotic.
* Lobeline, a bronchodilator.

Question 3

What are the Piperidinine alkaloids?

Answer 3

• 6-membered ring containing five carbons and one nitrogen:
• Nicotine, the precursor nicotinic acid (B3).
• Piperine (Piper nigrum L.). What is the impact of piperine? Piperine (piperidine amide). Pungent constituent of black pepper. Enhances absorption and bioavailability of certain herbal and conventional drugs. Lots of research done!! Reduce insulin resistance, antiinflam… etc etc
• Lobeline (Lobelia inflata L.).Lobelia inflata - more to come

Question 4

What is the impact of Lobelia inflata L?

Answer 4

Lobelia contains:
* Piperidine alkaloids: lobeline, lobelanine and lobelanidine.
* Lobeline is similar to nicotine but less potent - can be used as a substitute. Tastes like tobacco.
* Able to effect the nicotinic receptors on central, peripheral nervous system, muscle: responds to acetyl choline, nicotine and lobeline.

In small doses, a great respiratory stumulant
* Lobeline is a reflex expectorant at subemetic doses, a respiratory stimulant.
* Stimulates nicotinic receptor sites.
* Antispasmodic, bronchodilator.
* Expectorant mediated via adrenal cortex.
* Promotes the release of adrenalin and noradrenaline.

Many use it to help people to stop smoking.

Toxicology
* Vomiting, thus relatively safe.
* Symptoms: nausea, salivation, diarrhoea,
disturbed hearing and vision, mental confusion, marked weakness. Hypotension, the
pulse becomes weak, rapid, and irregular, difficulty breathing.

Question 5

What are the tropane alkaloids?

Answer 5

For example Atropine
Found in the Potato family
* CNS Effects.
* Anticholinergic, parasympatholytic:
* Reduce tremor and rigidity in mild Parkinson’s disease.
* Urinary frequency: may improve bladder muscle tone.
* Risk of overdose.

eg Hyoscyamine (levo-atropine)
* Parasympathetic depressant (blocks muscarinic receptors).
* Spasmolytic effect on bronchial and intestinal smooth muscle - can be used for asthma or cramps in digestive system, for emergency treatment
* Mydriatic - inhibits contraction of eye muscles (helps to look inside the eye)
* Reduces salivary and sweat gland secretions.
* Reduces rigidity and tremors of Parkinsonism.

Question 6

What plants contain them?

Answer 6

Only for acute, short episodes as very powerful on CNS especially

Atropa belladonna L.: Antispasmodic drug for GIT: Intestinal spasms, painful spasm of gallstones, kidney stones, enuresis and dysmenorrhoea. Tremor and rigidity of Parkinsonism, senile tremors. Excessive salivation, hyperhidrosis. Hananja mainly uses for gallstones.

Thornapple, Datura stramonium L: Traditionally used via smoking for asthma. Asthma, pertussis. Better for lung conditions as less drying, and can be used more safely than Belladonna for a longer period of time.

Henbane, Hyoscyamus niger L: Least potent. Used to relieve tremors: Parkinson’s and senile tremor. Prophylactic for motion sickness, Menière’s disease. Hananja usually uses for Parkinsons.

Question 7

What are the quinoline alkaloids?

Answer 7

Quinoline alkaloids
* Peruvian bark, Cinchona pubescens Vahl : quinine and quinidine. Historially delivered in wine.

Action in malaria
* Plasmodium parasite digests haemoglobin and releases free, toxic haem.
* To avoid destruction, the parasite then biocrystallizes haem (haemozoin).
* Quinoline inhibits haem biocrystallization.

More cinchona actions and side effects
* Skeletal muscle relaxant, febrifuge for colds, cardiac arrhythmias and influenza.
* S.E. tinnitus, skin rash, vertigo, bleeding, bruising and visual disturbances.

Question 8

What are the Isoquinoline alkaloids?

Answer 8

• Two fused 6-membered rings, one of which contains a nitrogen atom - often found in the Opium family
• Usually tetracyclic or pentacyclic.
• Isoquinolines metabolised from tryptophan, quinoline from tyrosine.

Papaveraceae, berberidaceae and ranunculaceae
* Boldine.
* Morphine, codeine.
* Berberine, hydrastine and palmatine.

One that contains is the California poppy, Eschscholzia californica Cham
* Analgesic, sedative, anxiolytic and antispasmodic. Not sure how it works!! Reacts with the CNS

Boldo, Peumus boldus Molina
* Contains boldine and isoboldine.
* Antioxidant, antispasmodic and cholagogue. Hananja says specific for gallbladder colic.

Boldine protects against liver disease. Also, other actions of boldine..
* Relaxes smooth muscle tissue.
* Antioxidant.
* Vasorelaxing, immuno- and neuro-modulator.
* Cholagogue and choleretic.
* Anti-inflammatory effect.

Question 9

What is the impact of Greater celandine, Chelidonium majus L.?

Answer 9

Greater celandine, Chelidonium majus L.
* Chelidonine, sanguinarine, coptisine and chelerythrine, protopine.
* Traditional reputation as a liver
herb.

Clinical trials using greater celandine
* Milk thistle, Silybum marianum L., Chelidonium and turmeric, Curcuma longa L. in human trial: increase in bile flow and pancreatic secretion. Not sure which herb is doing what!
* Beneficial for cramp, GIT, chronic bronchitis and whooping cough.
* Chelidonium and tumeric reduced right upper quadrant colicky pain in patients with biliary dyskinesia (gallbladder pains).
* An infusion of dried chelidonium used as an enema to treat intestinal polyps, found to be beneficial.

Question 10

Should you use fresh or dried Celandine?

Answer 10

Fresh or dried Celandine?
* The orange sap in alkaloids has an enzyme capable of breaking down nucleic acid (such as in viruses).
* Spasmolytic activity inconsistent: action reduced on prolonged storage.
* Chelidonium dried at 80°C preserved the levels of alkaloids found in the fresh plant.
* Chelidonium dried more slowly at 20-50°C, half of its alkaloids were lost.
* Lower levels of alcohol added to a fresh plant do not completely inhibit enzyme activity.

Question 11

What is Berberine?

Answer 11

Berberine (is a isoquinone alkaloid, a protoberberine)
* Berberine, a bright yellow, water-soluble alkaloid, has been widely studied - unusual as most are colourless and not water soluble.
* Found in goldenseal, Hydrastis canadensis
L., Mahonia spp., Berberis vulgaris L.,
Corydalis turtschaninovii Besser, Chelidonium spp., Sanguinaria canandensis L. and Eschscholzia californica.
* Goldenseal also contains hydrastine and
canadine which are synergistic with berberine.

Actions of berberine
Indications:
* Diabetes, diabetic nephropathy.
* Dislipidaemia.
* Fatty liver disease.
* Cardiovascular disease.
* Antimicrobial against a wide range of bacteria. Anti everything!
* Antioxidant and anticancer.

More effects of berberine
* Anti ulcer effect.
* Supports healthy bone metabolism.
* Increased leucocyte count in leukopenia in vivo.
* Radiation protective effect.
* External for burns.
* Renoprotective.

Question 12

What about isoquinone alkaloids ,Protopine, tetrahydropalmatine and palmatine?

Answer 12

Protopine, tetrahydropalmatine and palmatine
* Protopine: greater celandine, fumitory,
Fumaria officinalis L., Corydalis spp and opium poppy)
* Anti-inflammatory in vivo.
* Analgesic in vitro and in vivo.
* Tetrahydropalmatine (Corydalis): blocks postsynaptic dopaminergic receptors,
sedative and analgesic effects. Usually used for neuralgia and menstrual pain.
* Palmatine: in Coptis chinensis Franch.
and Corydalis spp: liver tonic, analgesic
and anti-inflammatory.