~Most alkaloids are precipitated from neutral or slightly acidic solution by Mayer's reagent (potassium mercuric iodide solution). Cream colored precipitate

Dragendorff's reagent (solution of potassium bismuth iodide) gives orange colored precipitate with alkaloids

Pg 1

~ Two distinct tropane alkaloid groups:
            1. Those found in Solanaceae ( flowering  plant 🌱 )

(the solanaceous tropane alkaloids

e.g. atropine type)
            2. Those from the Erythroxylaceae (flowering 🌳 )

(e.g. cocaine type)

pg 2

~Hyoscine hydrobromide is used in cancer treatment to prevent nausea and vomiting that results from movement of the head.

~It is a known anticholinergic, and therefore, prevents the toxic effects that can result due to accumulation of acetylcholine in the neuromuscular junctions and the parasympathetic nervous system.

pg 5 

~The stereochemistry at the tropane ester centre. In atropine, the tropic acid is joined to the tropane nucleus by an α linkage while in cocaine, linkage is β.

~Atropine contains tropic acid estermoiety while in cocaine, it is the benzoate ester that is present.

pg 7

~Brompton’s cocktail (cocaine and heroin in sweetened alcohol) widely used to control severe pain in terminal cancer patients.
~Compound play an important part in the development of other local anesthetics e.g. procaine

Adverse effects are:
~Fever & headache due to increased motor activity, vasoconstriction and increased blood pressure.

~Irregular heart beat, tachycardia, may lead to heart failure.
~Psychiatric disturbances, central stimulant addiction.

pg 8

~ Colchicine is non-basic, and does not form salts like other alkaloids.

Uses:
~In medicine, colchicine is used as a remedy against gout, a disease caused by the deposition of uric acid in the joints.
~It is an effective treatment for acute attacks. ( anti-inflammatory agent).

~Does not affect uric acid metabolism, which needs to be treated with other agents such as allopurinol.

~ highly toxic 
~ inhibit cell division


pg 14

~ Activation of k-opioid receptors is associated with spinal analgesia and miosis.

Effects of Morphine
1. Nausea, vomiting, constipation ( used in some anti- diarrhoea preparations e.g. kaolin and morphine).
2. Respiratory depression and high doses can cause death by respiratory failure.
3. Morphine crosses the placental barrier
4.Highly addictive. Methadone treatment has been useful in curing morphine addiction.

pg 16

urinary retention and constipation.

pg 17 

~ Valuable in certain neurological conditions, e.g. multiple sclerosis, tetanus and Parkinson’s disease, to temporarily relax rigid muscle and control convulsions.
~ Consist of tubocurarine and atricurarine.
 
pg 22

~ Prolongs the effect of endogenous acetylcholine; can be used as an antidote to anticholinergic poisons such as atropine.

pg 26

~ Water-insoluble group which contains peptide derivatives e.g. ergotamine (the peptide side chain is made up of analine, proline and phenylalanine).

       > Ergometrine (Ergonovine)
~Ergometrine used as an oxytocic since it causes strong muscular contraction.

~ Reduces bleeding because of vasoconstrictor effect; valuable after caesarian operation.
         
           > Ergotamine
~ Employed often in combination with caffeine for the treatment of migraine (by vasoconstriction of cerebral blood vessels).
~ Hydrogenation of the 9,10-double bond in the lysergic acid moiety yields dihydroergotamine.
This is employed as remedy for migraine. Often better tolerated by patients.

Pg 27

~ Cure for headache.

~ Have hallucinogenic effect
~ Hallucinogenic - drugs, plants, substances inducing hallucinations.
~ React with Diethylamine, C4H11N

pg 28

~ Lysergic acid is made from the tartrate salt of ergotamine derived from the ergot fungus on rye.

~ Only a small amount of ergotamine tartrate is required to produce LSD in large batches.

pg 29

~ Antipsychotic and antihypertensive.

~ First effective remedy for psychoses.

It acts by interfering with catecholamine storage, depleting levels of available neurotransmitters.

Prolonged use of the pure alkaloid reserpine has been shown to lead to severe depression in some patients.

2. Ajmaline and Ajmalicine
~ Ajmaline is used as a remedy for cardiac arrhythrimia while ajmalicine (also extracted from cantharanthus roseus)  is employed as an antihypertensive

pg 30 

~ Plant extracts have no effect on blood sugar levels in rabbits, but test animals succumbed to bacterial infection due to depleted white blood cells (leukopenia).
~ The plant (Catharanthus roseus) produces higher proportion of vinblastine than vincristine.

Fortunately possible to convert vinblastine into vincristine by controlled chromic acid oxidation or via a microbial N-demethylation using Stretomyces albogriseolus.

Catharanthine and vindoline, which are produced in much larger proportion, now possible to convert catharanthine and vindoline into vincristine in 40%.

                    Vinblastine/ Vincristine

~ These alkaloids have dimeric indole structures, composed of an indole and a dihydro indole unit catharanthine and vindoline moiety.
~ Both bind tightly to tubulin and inhibit the polymerization of tubulin into microtubules, preventing spindle formation in mitosis cells. 

This effectively stops the tumour cells from dividing, thus causing remission of the cancer.
~ Vinblastine used mainly in treatment of Hodgkin’s disease (a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes) a cancer affecting the lymph glands, spleen and liver. 

Vincristine has superior antitumour activity compared to vinblastine hence more important than vinblastine (especially in treatment of childhood leukemia, lymphomas, small cell lung cancer, cervical and breast cancer) but is more neurotoxic.

pg 31

~ Intense bitter taste and does not dissolve in water nor well in alcohol.

~ It is one of the most bitter substance in the world. 

~ Its taste is detectable in concentration as low  as 1 ppm It was used as a poison for rodents and other pests.

~ Very small doses can give a feeling of stimulation. 

~ In larger doses (30-100mg) strychnine is deadly poison, leading to violent muscular convulsions
~ Strychnine poisoning in humans can be fatal and can be introduced to the body by inhalation, swallowing or absorption through eyes or mouth.

~ Treatment involves giving depressant e.g. intravenous diazepam, to control the convulsion and giving an activated charcoal infusion to drink, to absorb any poison remaining within the digestive system.

~ It is a bitter alkaloid closely related to strychnine but is not as poisonous.

~ It is primarily used in the regulation of high blood pressure.

Chemically, structure of brucine is very similar to that of strychnine with methoxy groups at the aromatic ring rather than hydrogens

pg 32

~ Difference between isoquinoline and quinoline is position of Nitrogen atom.

pg 33

Almost insoluble in water, it dissolves readily in alcohol and other organic solvents.

~Quinine also has been used medicinally to:

~ Excessive dosage or continuous use of quinine may cause cinchonism .

~ Characterized by ringing in the ears, headache, dizziness, changes in blood pressure and even death.

~ Patients treated with quinine may also suffer from hypoglycaemia (especially if administered intravenously) and hypotension.
 
Mechanism of action of quinine
It is toxic to the malaria parasite, by interfering with the parasite’s ability to break down and digest haemoglobin, thus starving the parasite and/or causing the build-up of toxic levels of partially degraded haemoglobin in the parasite.

2. Quinidine - stereoisomer of quinine
~ Acts as an antiarrhythmic agent in the heart.

Side Effects of Quinidine

Quinidine can lead to increased blood levels and some anti-depressants effects.

Quinidine intoxication can lead to a collection of symptoms collectively known as cinchonism with tinnitus (ringing in the ears).
3. Chloroquine
~ Is a 4-aminoquinoline drug used in the treatment or prevention of malaria.

 ~ Used to suppress the disease process in rheumatoid arthritis.

Side-effects include:

pg 34

~ Pilocarpine is a cholinergic agent and stimulates muscarinic receptors in the eye, causing  constriction of the pupil (miosis) and contraction of ciliary muscle.

~ Used as hydrochloride or nitrate salts in eye drops for treatment of glaucoma.
~ Found to give relief for dryness of the mouth (xerostomia)

~ Pilocarpine is used to treat side effects arising from radiation treatment for head and neck cancer. 

Side effects

~Increased sweating.

~ Stimulate sweat glands in a sweat test to measure the concentration of chloride and sodium that is excreted in sweat.

~ Nausea, vomiting, bronchospasm, Increased bronchial mucus secretion, bradycardia, hypotension, and diarrhea.

pg 35