17-C) NON ISOQUINOLINES; AMARYLLIDACEAE ALKALOIDS AND TROPONOLONE RING AND

Question 1

AMARYLLIDACEAE ALKALOIDS. BRIEF INTRODUCTION

Answer 1

The bulbs of species from this family (often cultivated as ornamental plants)
are well-known for their toxic properties.

Their alkaloids derived from
aromatic amino acids arise by alternative modes of oxidative coupling of
precursors related to norbelladine. The different types depend on
the phenolic coupling of the precursor p-O-methylnorbelladine.
GALANTHAMINE; para-ortho oxidative coupling.

Question 2

AMARYLLIDACEAE ALKALOIDS. DRUGS

Answer 2

• Snowflakes (Bulb of Leucoju aestivum L.)
• Snowdrops (Bulb of Galanthus nivalis L.)

They are industrail sourcesof galanthamine, also obtained by synthesis.

Question 3

GALANTHAMINE (REMYNIL)

Answer 3

It is a competitive and reversible acetylcholinesterase inhibitor and as such has been used since 1950s in anesthesia as a curare reversal agent.
Galanthamine also acts centrally penetrating the blood-brain barrier to serve as a modulator of nicotinic cholinergic receptors, augmenting central
cholinergic neurotransmission.

Galanthamine produces an improvement of memory and intellectual functioning.

Therapeutic indications In the symptomatic treatment of mild to moderate . Alzheimer`s diseases.
Extended- release capsules.

Razadyne; administered one daily.
Dementia of vascular origin, recommmendation, later to be withdrawn.

Question 4

BIOSYNTHESIS OF COLCHICINE

Answer 4

Tyrosine -> Dopamine
Phyelalanine -> Trihydroxycinnamic aicd
Dopamine + trihydroxycinnamic acid -> Phenethylisoquinoline

Question 5

TROPOLONE RING ALKALOID- CONTAINING DRUGS

Answer 5

Autumm Crocus, Meadow Saffron, Colchicum-
-Bulb and seed of Colchicum autummale
-Glory Lily; gloriosa superba L
Whole plant, specially in the bulb 0.9% colchicine

It is widely cultivated as an ornamental garden plant, and is grown for drug use. The principal alkaloid, colchicine (0.8% in the seed, and 0.6% in the corm), does not display any bascity (amide), and does not form well - defined salts.

Question 6

SOLUBILITY OF COLCHICINE

Answer 6

The principal alkaloid of Colchicum autummale is colchicine (0.8% in the seed, and 0.6% in the corm), does not display any bascity (amide), and does not form well - defined salts. It hs a particular solubility; : soluble in water, alcohol or chloroform. It is a
weak base and may be extracted from either acid or alkaline solutions
by chloroform. Sensitive to light, colchicine produces a yellow colour
by treating the crude drug with 60-70% of sulphuric acid or
concentrated hydrochloric acid.
Cochicine is also used in biological experiments to produce polyploidy
or multiplication of the chromosomes in the cell nucleus.

Question 7

PHARMACOLOGICIAL ACTION OF COLCHICINE (CHARACTERISTICS)

Answer 7

•Antimitotic: blocks mitosis at the metaphase stage by preventing the formation of the mitotic spindle. It binds to tubulin and interferes in the
assembly of microtubules.
•Specific anti-inflammatory to the microcrystalline arthritis caused by
sodium urate crystals. It is an effective treatment for acute attacks, but it is very toxic, and this restricts its general use.
•Highly toxic, it has assayed as antitumor (as potential anticancer) agent, though they are too toxic for medicinal use.

Question 8

PHARMACOLOGICIAL ACTION OF COLCHICINE (INDICATIONS)

Answer 8

•Treatment of the acute attack of gout, until disappearance of pain or
appearance of digestive symptoms. Oral way 24-48 hours.
•Prophylaxis to prevent the acute attack of gout in chronic patients.
Colchicine is frequently prescribed in tablets form and transdermal
preparation containing colchicine.

Question 9

SEMISYNTHETIC DERIVADIVES OF COLCHICINE

Answer 9

Thiocolchicoside; Adagur

Trhiocolchicoside + acetaminophen -> muscle relaxant; torticollis, back pain…