2. , Poisons & Antidotes: Strychnine
Botanical: Strychnos Nux-vomica (LINN.)
Family: N.O. Loganiaceae
---Synonyms---Poison Nut. Semen strychnos. Quaker Buttons.
---Part Used---Dried ripe seeds.
---Habitat---India, in the Malay Archipelago. ---Description---A medium-sized tree with a short,
crooked, thick trunk, the wood is white hard, close grained, durable and the root very bitter.
Branches irregular, covered with a smooth ash-coloured bark; young shoots deep green, shiny;
leaves opposite, short stalked, oval, shiny, smooth on both sides, about 4 inches long and 3 broad;
flowers small, greeny-white, funnel shape, in small terminal cymes, blooming in the cold season
and having a disagreeable smell. Fruit about the size of a large apple with a smooth hard rind or
shell which when ripe is a lovely orange colour, filled with a soft white jelly-like pulp containing
five seeds covered with a soft woolly-like substance, white and horny internally. The seeds are
removed when ripe, cleansed, dried and sorted; they are exported from Cochin, Madras and other
Indian ports. The seeds have the shape of flattened disks densely covered with closely appressed
satiny hairs, radiating from the centre of the flattened sides and giving to the seeds a
characteristic sheen; they are very hard, with a dark grey horny endosperm in which the small
embryo is embedded; no odour but a very bitter taste.
3. ---Medicinal Action and Uses---The propertiesof NuxVomica are substantially those of the
alkaloid Strychnine.The powdered seeds are employed in atonic dyspepsia.The tincture of Nux
Vomica is often used in mixtures - for its stimulant action on the gastro-intestinal tract. In the
mouth it acts as a bitter, increasing appetite; it stimulates peristalsis, in chronic constipation
due to atony of the bowel it is often combined with cascara and other laxatives with good
effects. Strychnine, the chief alkaloid constituent of the seeds, also acts as a bitter, increasing
the flow of gastric juice; it is rapidly absorbed as it reaches the intestines, after which it exerts
its characteristic effects upon the central nervous system, the movements of respiration are
deepened and quickened and the heart slowed through excitation of the vagal centre.The
senses of smell, touch, hearing and vision are rendered more acute, it improves the pulse and
raises blood pressure and is of great value as a tonic to the circulatory system in cardiac failure.
Strychnine is excreted very slowly and its action is cumulative in any but small doses; it is much
used as a gastric tonic in dyspepsia.The most direct symptom caused by strychnine is violent
convulsions due to a simultaneous stimulation of the motor or sensory ganglia of the spinal
cord; during the convulsion there is great rise in blood pressure; in some types of chronic lead
poisoning it is of great value. In cases of surgical shock and cardiac failure large doses are given
up to 1/10 grain by hypodermic injection; also used as an antidote in poisoning by chloral or
chloroform. Brucine closely resembles strychnine in its action, but is slightly less poisonous, it
paralyses the peripheral motor nerves. It is said that the convulsive action characteristic of
strychnine is absent in brucine almost entirely. It is used in pruritis and as a local anodyne in
inflammations of the external ear.
4. --Preparations and Dosages---Strychnine should not be administered in liquid form combined
with bromides, iodides or chlorides, there being a risk of formation of the insoluble
hydrobromide, etc.
NuxVomica, 1 to 4 grains. Extract of NuxVomica, B.P., 1/4 to 1 grain. Extract of NuxVomica,
B.P. 1885, 1/4 to 1 grain. Extract of NuxVomica, U.S.P., 1/4 grain. Liquid extract of NuxVomica,
B.P., 1 to 3 minims. Fluid extract of NuxVomica, U.S.P., 1 minim.Tincture of NuxVomica, B.P., 5
to 15 minims.Tincture of NuxVomica, B.P. 1885, 10 to 20 minims.Tincture of NuxVornica,
U.S.P., 10 minims. Strychnine, B.P., 1/6 to 1/15 grain. Hypodermic injection of strychnine.
Solution of Strychnine Hydrochloride, B.P., 2 to 8 minims.Acid Strychnine Mixture, B.P.C., 1/2
to 1 fluid ounce.
-Poisoning and Antidotes---In cases of poisoning by strychnine an emetic or the stomach
pump should be used at once and tannin or potassium permanganate given to render the
strychnine inactive.Violent convulsions should be controlled by administration of chloroform or
large doses of chloral or bromide. Urethane in large doses is considered an antidote. Amyl
nitrite is also useful owing to its rapid action during the convulsion, and in absence of
respiration 3 to 5 minims may be hypodermically injected.
---Other Species---
Strychnos tieute, a clumbing shrub growing in Java, gives a juice termed Upas tieute, said to be
used by the natives as an arrow poison; it produces death by violent convulsions, the heart
stopping before respiration.
S. toxifera yields the deadly poison Curare (Woorari or Urari) used by the natives of British
Guiana.
5. S. ligustrina, the wood of which contains brucine, as does the bark.
S. pseudo is found in the mountains and forests of India. It supplies the seeds known as clearing
nuts.The fruit is black, the size of a cherry, containing only one seed; fruit and seeds are used
medicinally in India and also to clear muddy water, the seeds being rubbed for a minute inside
the vessel and the water then allowed to settle; their efficiency depending on their albumen
and casein contents acting as a fining agent similar to those employed to clarify wine and beer.
S. innocua.The fruit and pulp are harmless and are eaten by the natives of Egypt and Senegal.
S. Ignatii is found in the Philippines, the seeds containing strychnine and brucine, strychnine
being present in greater quantity than in NuxVomica. A tincture made from the beans is official
in the British Pharmacopoeia Codex.
---Constituents---Nux Vomica contains the alkaloids, Strychnine and Brucine, also traces of
strychnicine, and a glucoside Loganin, about 3 per cent fatty matter, caffeotannic acid and a trace
of copper. The pulp of the fruit contains about 5 per cent of loganin together with the alkaloid
strychnicine.
6.
7. F. Strychnine
Biological Sources It is abundantly found in the seeds of Strychnos NuxVomica L.
(Loganiaceae) (NuxVomica, Strychnine); beans of Strychnos ignatti Berg.
(Loganiaceae); roots of S. cinnamomifolia Thw.; seeds, bark and wood of S.
colubrina Linn.; and plant of S. malaccensis Benth. (Syn: S. gautheriana Pierre).
Chemical Structure
Strychnidine-10-one; (C21H22N2O2)
8. Salient Features
1. Strychnine contains two N-atoms even then it happens to be a mono-acidic base.
2. Strychnine readily forms a variety of salts, such as: nitrate, N6-oxide, phosphate and
sulphate. Interestingly, the N-atom which is specifically involved in the salt formation is the
one that is located farthest from the aromatic benzene ring.
3. The second N-atom is strategically positioned as an amide nitrogen; and, therefore, it
does not exhibit any basic characteristics.
Isolation Strychnine may be isolated from the seeds of S. nux vomica by adopting the
following steps sequentially:
1. The seeds of nux vomica are dried, ground and sieved which are mixed with an
adequate quantum of pure slaked lime and made into a paste by adding a requisite
amount of water. The wet mass thus obtained is dried at 100°C and extracted with hot
chloroform in a continuous extractor till the extraction is completed.
2. The alkaloids are subsequently removed from the chloroform solution by shaking with
successive portions of dilute sulphuric acid (2N). The combined acid extracts are filtered to
get rid of any foreign particles or residue.
3. To the resulting acidic filtrate added an excess of ammonia to precipitate the alkaloids
(strychnine + brucine).
4. The precipitate is extracted with ethanol (25% v/v) several times which exclusively
solubilizes brucine, and ultimately leaves strychnine as an insoluble residue.
5. The residue containing strychnine is filtered off and is finally purified by repeated
recrystallization from ethanol.
9. Characteristic Features
1. It is obtained as brilliant, colourless cubes from a mixture of chloroform and ether
having mp 275-285°C, and d18 1.359.
2. Its specific optical rotation [α]18
D-104.3° (C = 0.254 in ethanol); [α]25
D-13° (C = 0.4 in
chloroform).
3. Its dissociation constant pKa (25°) 8.26.
4. It has uvmax (95% ethanol); 2550, 2800, 2900 Å (E1% 1cm 377, 130, 101).
5. Solubility Profile: 1g dissolves in 182 ml ethanol, 6.5 ml chloroform, 150 ml
benzene, 250 ml methanol, 83 ml pyridine; and very slightly soluble in water and ether.
6. A solution of strychnine containing 1 part in 700,000 parts of water gives a distinct
bitter taste.
Identification Tests Strychnine may be identified either by specific colour tests or by
specific derivatives:
(a) Colour Tests
1. Sulphuric Acid-Dichromate Test: Strychnine (5-10 mg) when dissolved in a few
drops of concentrated sulphuric acid and stirred with a crystal of pure potassium
dichromate [K2Cr2O7] it gives an instant reddish-violet to purple colouration.
Note: Strychnine derivatives will also give this test except strychnine nitrate.
2. Mandelin’s Reagent Test: Strychnine or its corresponding salt when treated
with Mandelin’s Reagent* it gives rise to a violet to blue colouration.
3. Ammonium Vanadate (V) Test: Strychnine or its salt when treated with a saturated
solution of ammonium vanadate, it produces a violet to blue colouration.
4. Nitric Acid Test: Strychnine on being treated with a trace of HNO3 (conc.) yields an
instant yellow colouration.
10. Note: A similar test with Brucine gives an intense orange-red colouration. It may be used to
differentiate between strychnine and brucine.
(b) Strychnine Derivatives: The various important strychnine derivatives are as given under:
1. Strychnine Nitrate (C21H23N3O5): It is obtained as colourless, odourless needles or while
crystalline powder 1g dissolves in 42 ml water, 10 ml boiling water, 150 ml ethanol, 80 ml ethanol at
60°C, 105 ml chloroform, 50 ml glycerol; and insoluble in ether. It shows a pH ~ 5.7.
2. Strychnine N6– Oxide (C21H22N2O3): It is obtained as monoclinic prisms from water
which decompose at 207°C. It has pK value 5.17. It is found to be freely soluble in ethanol,
glacial acetic acid, chloroform; fairly soluble in water; sparingly soluble in benzene; and
practically insoluble in ether and petroleum ether.
3. Strychnine Phosphate (C21H25N2O6P): It is usually obtained as its dihydrate salt (2O6P.2H2O)
which is colourless or while crystals or white powder. 1g dissolves in slowly in ~ 30 ml water, more
soluble in hot water, and slightly soluble in ethanol. The aqueous solution is acidic to litmus.
4. Strychnine Sulphate (C42H46N4O8S): It normally crystallizes as pentahydrate
[2C21H22N2O2.H2SO4.5H2O]. It is colourless, odourless, very bitter crystals or white crystalline powder.
It effloresces in dry air and loses all its water of crystallization at 100°C. It shows mp when anhydrous
~ 200°C with decomposition. 1g dissolves in 35 ml water, 7 ml boiling water, 81 ml ethanol, 26 ml
ethanol at 60°C, 220 ml chloroform, 6 ml glycerol, and insoluble in ether. A 1 : 100 solution shows pH
5.5.
5. Strychnine Gluconate Pentahydrate (C27H34N2O9.5H2O): Its crystals darken above 80°C. It is
soluble in 2 parts water ~ 40 parts ethanol. The aqueous solution is found to be neutral.
6. Strychnine Glycerophosphate Hexahydrate (C45H53N4O10P.6H2O): 1g dissolves in ~ 350 ml
water, ~ 310 ml ethanol; slightly soluble in chloroform; and very slightly soluble in ether.
7. Strychnine Hydrochloride Dihydrate (C21H23ClN2O2.2H2O): It is obtained as trimetric prisms
which are efflorescent in nature. 1g dissolves in ~ 40 ml water, ~ 80 ml ethanol, and insoluble in ether.
The pH of a 0.01 M solution is 5.4.
11. Uses
1. Strychinine is extremely interesting pharmacologically and is regarded as a valuable
tool in both physiologic and neuroanatomic research.
2. It is extremely toxic, and functioning as a central stimulant.
3. It causes excitation of all parts of the central nervous system and blocks inhibitory
spinal inpulses at the post synaptic level. This may lead to an exaggeration in reflexes
ultimately leading to tonic convulsions.
4. The drug is rarely used in modern medical practice but is utilized as a vermin killer
i.e., animal or insect killer.
5. It is used chiefly in poison baits for rodents.
The biosynthetic pathway leading to vinblastine and vincristine is supposedly involve
the following vital steps:
1. An oxidative reaction on catharanthine, catalysed by an enzyme peroxidase, thereby
producing a peroxide that aptly loses the peroxide as a leaving group, ultimately breaking
a carbon-carbon covalent bond as shown in the diagram given below.
2. The intermediate electrophilic ion is attacked on to the conjugated iminium system by
the vindoline, whereby C-5 of the indole nucleus being appropriately activated by the –
OCH3 moiety located at C-6, and also by the N-atom present in the indole ring.
3. The resulting adduct is subsequently reduced in the dihydropyridinium ring by NADH*-
dependent 1, 4-addition thereby giving rise to the substrate for hydroxylation.
4. Ultimately, reduction of the above resulting product generates vinblastine.
5. The oxidized product from vinblastine, with its N-formyl moiety rather than N-methyl
on the vindoline fragment, may finally yield vincristine.
12. Passiflora or Passion flower
Scientific name: Passiflora incarnata
Other names: Passion flower, Passion vines.
The Passion flower is a plant with a permanent woody stem that can reach up to 10
m.The axillary pedicle grows to 8 cm and holds only a flower. Flowers are lined with a
diameter of 5 to 9 cm.The five sepals are gray on the outside and white inside. Has a
secondary corolla within the petals consisting of a 4-fiber ring arranged radially in the
axis of the flower, which are white on the inside and purple in the outside.The ovary
has 3 carpels and 3 styles, which end in a thick stigma.The 5 stamens are bound to the
base.
Parts used:The whole or fractional plant and the aerial parts.The yellow pulp of the
berries is edible. Some related species are also edible or have healing properties.
Passion Flower is originative from the southeastern part of North America untill
Argentina and Brazil. It is grown as an ornamental plant in Europe.
13.
14. Active ingredients of Passiflora or Passion Flower
The main active ingredients of Passiflora are:
Flavonoids: quercetol, kaempferol, apigenin, luteolin;
C-
heteroside: vitexin, saponaroside, schaftoside, isoschaftoside, isovitexin, isoorientin.
Phytosterols: sitosterol, stigmasterol;
maltol;
Traces of cyanogenicheterosides: ginocardina.
Traces of essential oil with a composition little studied.
Dry drug must contain at least 0.3% (Pharmacopoeia Helvetica) or 0.4% (German
Pharmacopoeia) of flavonoids expressed as hyperoside, or at
least 0.8% of flavonoids in vitexin (E.S.C.O.P.)
The presence of harmaline, frequently indicated, has not been properlyconfirmed.
15. RAUWOLFIA ROOT (Rauwolfia serpentina)
Latin: Rauwolfia serpentina
Sanskrit: Sarpaghandha
African: Numerous (R. vomitoria species)
Chinese: Lu fu mu (various species)
English: Rauwolfia / Indian snakeroot
WHAT IT DOES: Rauwolfia root is bitter in taste and cooling in action. It lowers blood
pressure, tranquilizes the mind, and promotes sleep.
RATING: Red, due to safety issues.
SAFETY ISSUES: Use only under the guidance of a trained physician or herbalist in
proper dosage. Do not use in pregnancy, breastfeeding, or depression. May
exacerbate symptoms of Parkinson's Disease. Do not combine with alcohol,
barbiturates (Pfeifer et al., 1976), SSRIs, blood-pressure lowering agents such as beta-
blockers, unless under guidance.
16.
17. Rauwolfia serpentina is a safe and effective treatment for hypertension.The plant was
used by many physicians throughout India in the 1940s and then was used throughout
the world in the 1950s, including in the United States and Canada. It fell out of
popularity when adverse side effects, including depression and cancer, became
associated with it.This author reviews the scientific literature with regard to the use
of Rauwolfia and the treatment of hypertension.The author reviews the plant’s
botany, chemistry, and pharmacology and provides a researched and documented
method of action for the active ingredients.With special emphasis on the plant’s role
in treating high blood pressure, the author looks at medical uses of the plant, critically
examining its adverse side effects, toxicology, and carcinogenicity.The author refutes
the association between the plant and carcinogenicity and discusses the importance
of correct dosing and of screening patients to minimize the occurrence of depression.
He concludes with the recommendation of use of low dose Rauwolfia (LDR) for
suitable patients with hypertension.The plant provides clinicians with a safe and
effective adjunct to pharmaceuticals in the treatment of high blood pressure.
18. Rauwolfia (Rauwolfia serpentina) is an evergreen shrub that is a member of the
dogbane or Apocynaceae family.1 More than 100 species are included in
the Rauwolfia genus, and they are native to tropical and subtropical regions of the
world, including Europe, Africa,Asia,Australia, and the Central and South
Americas.2 Rauwolfia serpentina is native to the moist, deciduous forests of
southeastAsia, including India, Burma, Bangladesh, Sri Lanka, and Malaysia.3The
plant usually grows to a height between 60 and 90 cm and has pale green leaves that
are 7 to 10 cm long and 3.5 to 5.0 cm wide.The leaves are elliptical or lanceolate
shaped and occur in whorls of 3 to 5 leaves.The plant has many shiny, black or purple,
round fruits that are approximately 0.5 cm in diameter. It also has small pink or white
flowers.The plant has a prominent tuberous, soft taproot that reaches a length
between 30 and 50 cm and a diameter between 1.2 and 2.5 cm.4
19. Chemical Composition
Rauwolfia contains many different phytochemicals, including alcohols, sugars and glycosides,
fatty acids, flavonoids, phytosterols, oleoresins, steroids, tannins, and alkaloids.The most
important alkaloids found in the plant are indole alkaloids, with more than 50 of those alkaloids
having been isolated in the plant.9 Indole alkaloids are a group of nitrogenous compounds that
are derived from the amino acid tryptophan.They share a common 5 and 6 carbon heterocyclic
ring structure with 1 nitrogen molecule.10
All parts of the plant, including the stem and leaves, contain indole alkaloids, but they are
found in highest concentration in the bark of the root.11The identified indole and indole
alkaloids include ajmalidine, ajmaline, ajmalinine, ajmalicine, aricine, canescine, coryanthine,
deserpidine, isoajmaline, isoserine, isoserpiline, lankanescine, neoajmaline, papaverine,
raubasine, raucaffricine, rauhimbine, rauwolfinine, recanescine, rescinnamine, reserpiline,
reserpine, reserpinine, sarpagine, serpentine, serpentinine, thebaine, yohimbine, and
yohimbinine.12,13
The exact concentration of alkaloids varies. One study found that the yield of total alkaloids
ranged from 0.8% to 1.3% of the dry weight of the plant.12 Another study put the total yield of
alkaloids between 0.7% to 3.0% of the root content.4The maximum alkaloid content detected
in regenerated roots was 3.3%.13 Other species in the Rauwolfia genus have been used in place
of R serpentina, including Rauwolfia vomitoria and Rauwolfia caffra from Africa and Rauwolfia
heterophylla and Rauwolfia tetraphylla from Central and South America.Woodson et al12 found
that the species of the same genus contained variable quantities of indole and indole alkaloids
and could be used as suitable alternatives to R serpentina.
20. Chemical composition
Rauvolfia serpentinaThe plant contains more than 50 different alkaloids which belong
to the monoterpenoid indole alkaloid family.The major alkaloids
are ajmaline, ajmalicine, ajmalimine, deserpidine, indobine, indobinine, reserpine, res
erpiline, rescinnamine, rescinnamidine, serpentine, serpentinine and yohimbine.[7]
Medicinal uses[edit]
The extract of the plant has been used for millennia in India – Alexander the
Great administered this plant to cure his general Ptolemy I Soter of a poisoned
arrow.[citation needed] It was reported that MahatmaGandhi took it as
a tranquilizer during his lifetime.[8] It has been used to treat insect stings and the bites
of venomous reptiles.[citation needed] The plant also contains reserpine, was used to
treat high blood pressure and mental disorders including schizophrenia, and had a
brief period of popularity for that purpose in theWest from 1954 to 1957.[9] R.
serpentina is also known for its antimicrobial, antifungal, anti-
inflammatory, antiproliferative, antidiuretic and anticholinergicactivities.[7]
Recent research has proved that Rauwolfia serpentina exhibits activity against drug-
resistant tumor cells.[10]
It is one of the 50 fundamental herbs used in traditional Chinese medicine, where it
has the name shégēn mù (Chinese: 蛇根木) or yìndù shémù (Chinese: 印度蛇木).
21. Ergot; Rye Ergot: Secale cornutum.
Biological source:
It is the dried sclerotinum of a fungus, Claviceps purpureaTulasne, developing in the
ovary of rye plant, Scale cereale. Ergot should yield about 0.15% of the total alkaloids
calculated as ergotoxine.
Family:
Clavicipitaceae
Cultivation:
The life cycle of the fungus, claviceps purpurea, which is a parasite, passes through
the following characteristics stages:
Chemical constituents:
1. Most important alkaloids are
Ergometrine group (Water soluble):
Ergometrine,
Ergometrinine.
Ergotamine group (water -insoluble):
Ergotamine
Ergotaminine
Ergosine.
Ergosinine.
22. Ergotoxine group (Water-insoluble):
Ergocristine
Ergocristinine
Ergocryptine
Ergocryptinine
Ergocornine
Ergocorninine.
2. Alkaloids obtained from lysergic acid are physiological active.
3. Histamine, tyramine, and other amine,
4. Putriscine, cadaverine, agmatine, amino acids, colouring matter.
5. Sterols like ergosterol and fungisterol,
6. Elymoclavine, sclerythrin, ergonovine,
7. Clavicepsin, ergoflavin, ergotic acid betaine, alkaloid
8. Clavine, mannitol, lactic acid and succinic acid.
ChemicalTests:
Ergot under UV light shows a red-coloured fluorescence. Ergot powder is extracted with a
mixture of CHCI3 and sodium carbonate.The CHCI3 layer is separated and a mixture of p-
dimethylaminobenzaldehyde, H2SO4 and 5% ferric chloride solution is added. A deep blue
colour is produced.
23. Uses:
1. Ergot is oxytocic, vasoconstrictor and abortifacient and used to assist delivery and to reduce
post-partum haemorrhage.
2. Ergotamine is used to treat migraine.
3. Lysergic acid diethylamine, obtained by partial synthesis from lysergic acid is a potent
specific psychotomimetic.
4. Ergometrine is oxytocic and used in delivery.
It is stimulates the tone of uterine muscles and prevent post-partum haemorrhage.
1. Isolation of water- soluble ergot alkaloids:
(i) Ergot powder is de-fatted with light petroleum, allowed to dry in air, and mixed thoroughly
with sodium bi carbonate.
(ii)The mass is made damp, by adding water drop by drop, with stirring.
(iii)The mixture is transferred to a percolator and extracted with peroxide free ether containing
5% ethyl alcohol. Extraction of the alkaloids is carried out best by drawing off 10 ml of percolate
at interval of the one hour until 70 ml is collected.
(iv)The powder is left in contact with the solvent overnight, and percolation is continued as
above until another 100 ml percolate is collected.The percolation is once more stopped and the
powder is allowed to remain in contact with the solvent overnight.The extraction is completed
by drawing off portion of percolate at 30 minute interval until the last percolate shows negative
reaction for Alkaloidal tests.
(v)The ethereal extract is transferred to a separating funnel and the alkaloids removed by
shaking with six 10 ml portion of 5% lactic acid.
(vi)The combined extracts are collected and dried in a vacuum drier.
24. 2. Isolation of Ergotamine:
(i) Powder drug of ergot is defatted with petroleum ether (40- 60°).
(ii)The marc consisting of the defatted powdered ergot is thoroughly mixed with aluminium
sulphate and water so as to fix the alkaloids by converting them into the double salts.
(iii)The resulting Alkaloidal double salts are continuously extracted with hot benzene to
removes the Alkaloidal exclusively on one hand; and the unwanted substances e.g. ergot oil,
soluble acid, neutral substances like phytosterol, colouring matter and organic acid on the
other.
(iv)The benzene is removed under vacuo and residue thus obtained is stirred for several hours
with a large volume of benzene and subsequently made alkaline by passing NH3gas.
(v)The resulting solution is filtered and the benzene and subsequently under vacuum and
ergotamine crystallizes out.
(vi) An additional quantity of ergotamine may also be crystallized from the mother liquour by
treatment with petroleum ether.
(vii) Ergotamine may be further purified by crystallization from aqueous acetone.
