STRYCHNINE Strychnine is an alkaloid that is found in Strychnos nux-vomica (Loganiaceae). It causes excitation of all parts of the central nervous system, with a characteristic motor pattern. Strychnine is a competitive antagonist at inhibitory neurotransmitter glycine receptors in the spinal cord, brain stem, and higher centers. It thus increases neuronal activity and excitability, leading to increased muscular activity. Since strychnine also causes convulsions in decerebrate animals, the convulsion is termed a “spinal convulsion”, but other parts of the central nervous system are also stimulated by doses that produce motor manifestations in a decerebrate animal. Strychnine does not selectively stimulate the medulla and cannot therefore be regarded as a useful analeptic drug. There are three main ways that strychnine can enter the body: inhalation, ingestion, and broken skin. PICROTOXIN Picrotoxin is a non-nitrogenous plant derivative that is a powerful stimulant of all parts of the central nervous system, acting on the chloride ionophore–gamma-aminobutyric acid (GABA) complex in a manner opposite to that of barbiturates. It may also be an antagonist at 5HT3A receptors. It has been used to induce seizures and other nervous system effects in experimental animals and in humans to treat barbiturate toxicity. A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the gamma-aminobutyric acid-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.

1. STRYCHNINE
&
PICROTOXIN
Assignment-612

2. STRYCHNINE
Assignment-612

3. Assignment-612
STRYCHNINE
Strychnine is an alkaloid that is found in Strychnos nux-
vomica (Loganiaceae). It causes excitation of all parts of
the central nervous system, with a characteristic motor
pattern. Strychnine is a competitive antagonist at
inhibitory neurotransmitter glycine receptors in the spinal
cord, brain stem, and higher centers.

4. Assignment-612
It thus increases neuronal activity and excitability, leading to
increased muscular activity. Since strychnine also causes
convulsions in decerebrate animals, the convulsion is termed a
“spinal convulsion”, but other parts of the central nervous system
are also stimulated by doses that produce motor manifestations
in a decerebrate animal.

5. Assignment-612
Strychnine does not selectively stimulate the medulla and
cannot, therefore, be regarded as a useful analeptic drug.
There are three main ways that strychnine can enter the
body: inhalation, ingestion, and broken skin.

6. Assignment-612
STRYCHNINE THE MEDICINE
Despite the dangerous nature of the drug, reports of its
therapeutic value have been described. Medicinal uses appear
to be linked with its ability to induce muscle contraction:

7. Assignment-612
 Paralysis: The most common use appears to be in patients
with paralyzed or palsied limbs. The strychnine was mixed
with a tiny quantity of dilute sulphuric acid and up to fifty
parts glycerin before being rubbed over the limb(s) or
down the spinal cord. This would heighten the sensitivity
of the nerves to stimulation.
 Visual Disturbances: In its liquid form, strychnine was used
as eye drops to produce contraction of the pupil and induce
muscle accommodation. In patients with loss of vision, it
was injected directly into the eye to induce muscle
contraction.

8. Assignment-612
 There is a record to suggest that strychnine could be
used in patients with irritable nervous systems. Few
details are given although it suggested that the starting
dose should be one twenty-fourth of a grain. This could
be increased to one-sixteenth or one-twelfth of grain
until the desirable effects were observed.
 Other: Mention has been made of it being used in
patients with rectal prolapse (as an injection). This
was presumably to hold the rectum in place and
prevent protrusion.

9. Assignment-612
The best form of administration was as a pill. If this had no
effect an alternative form of administration was to make it into
a solution. If patients were able to tolerate the bitterness, it
could be dissolved in water containing enough acetic, diluted
sulphuric, or muriatic acid, to produce a clear liquid. Incredibly,
it could also be dosed on children, where it was suggested, it is
made up with a teaspoon of syrup.

10. Assignment-612
The pharmacopeia’s of the time carried a warning saying that
strychnine should be prescribed and administered with the
greatest caution. Indeed, many instances of death are on record
as a result of careless dispensing or administration.

11. Assignment-612
PHARMACOKINETICS:

12. Assignment-612
Strychnine is absorbed rapidly after ingestion or nasal inhalation
and distributed rapidly into the tissues. It has low plasma protein
binding and a large volume of distribution (Vd estimated at 13
L/kg in one case report). Strychnine is metabolized by the hepatic
cytochrome P-450 microsome system to a major metabolite,
strychnine N-oxide, by first-order kinetics. Elimination is
predominantly extrarenal, with an elimination half-life of about
10–16 hours

13. Assignment-612
INDICATIONS

14. Assignment-612
Strychnine can be given in adjunctive therapy as an
alternative drug of choice in
• Bronchial asthma,
• Constipation,
• Diabetes mellitus,
• Diarrhoea,
• hyperglycemia,
• Ophthalmic, Pain,
• Urinary tract disorder.

15. Assignment-612
CONTRAINDICATIONS

16. Assignment-612
Strychnine is contraindicated in conditions like Excessive reflex
irritability, Acute inflammatory conditions of the spinal cord.
Strychnine acts as a powerful stimulating of the central nervous
system. It blocks the inhibitory or strychnine-sensitive glycine
receptor. When glycine receptors are activated, chloride enters
the neuron via ionotropic receptors, causing an Inhibitory
postsynaptic potential (IPSP). Strychnine is a strong antagonist at
ionotropic glycine receptors. Death is usually due to asphyxiation
resulting from continuous spasms of the respiratory muscles.

17. Assignment-612
METABOLISM
METABOLISM

18. Assignment-612
Strychnine is absorbed very rapidly through the gastrointestinal
tract, the respiratory tract, and intact skin. In addition, it is well
absorbed when given via the parenteral route (subcutaneous or
intranasal). This alkaloid is very lipophilic and is thus rapidly
distributed throughout the body.
The first symptoms usually appear within 5 minutes to 1 hour after
exposure, depending on the dose, the route of exposure, and the
general medical health of the person exposed. It undergoes rapid
and extensive metabolism by hepatic cytochrome P-450 2B and it
does not seem to have an accumulative effect.

19. Assignment-612
SIDE EFFECTS
• The severe or irreversible adverse effects of Strychnine, which
give rise to further complications include Tremors, Severe
spasms.
• Strychnine produces potentially life-threatening effects which
include Respiratory arrest, Painful convulsions. which are
responsible for the discontinuation of Strychnine therapy.
• The symptomatic adverse reactions produced by Strychnine are
more or less tolerable and if they become severe, they can be
treated symptomatically, these include Twitching and Stiffness
of the face and legs.

20. Assignment-612
PICROTOXIN

21. Assignment-612
Picrotoxin is a non-nitrogenous plant derivative that is a powerful
stimulant of all parts of the central nervous system, acting on the
chloride ionophore–gamma-aminobutyric acid (GABA) complex in
a manner opposite to that of barbiturates. It may also be an
antagonist at 5HT3A receptors. It has been used to induce seizures
and other nervous system effects in experimental animals and in
humans to treat barbiturate toxicity.

22. Assignment-612
A noncompetitive antagonist at GABA-A receptors and thus a
convulsant. Picrotoxin blocks the gamma-aminobutyric acid-
activated chloride ionophore. Although it is most often used as a
research tool, it has been used as a CNS stimulant and an antidote
to poisoning by CNS depressants, especially barbiturates.

23. Assignment-612
INDICATION
Used internally for relieving respiratory distress. Also, for used as
an antidote in poisoning by CNS depressants, especially
barbiturates.

24. Assignment-612
PHARMACODYNAMICS
Picrotoxin is a toxin obtained from the seeds of the shrub Anamirta
cocculus. It is used as a central nervous system stimulant, antidote,
convulsant, and GABA (gamma-aminobutyric acid) antagonist. It is a
noncompetitive antagonist at GABAA receptors and thus a
convulsant. Picrotoxin blocks the GABA Activated chloride
ionophore. Although it is most often used as a research tool, it has
been used as a CNS stimulant and an antidote to poisoning by CNS
depressants, especially barbiturates.

25. Assignment-612
MECHANISM OF ACTION

26. Assignment-612
Picrotoxin antagonizes the GABAA receptor channel directly,
which is a ligand-gated ion channel concerned chiefly with the
passing of chloride ions across the cell membrane. Therefore,
picrotoxin prevents Cl- channel permeability and thus promotes
an inhibitory influence on the target neuron. Picrotoxin reduces
conductance through the channel by reducing not only the
opening frequency but also the mean open time.

27. Assignment-612
Picrotoxin also antagonizes GABAC receptors (also called GABAA-
rho receptors) but the result of this action is not known. The
GABAC receptor is also linked to chloride channels, with distinct
physiological and pharmacological properties. In contrast to the
fast and transient responses elicited from GABAA receptors,
GABAC receptors mediate slow and sustained responses.

28. Assignment-612
TOXICITY
Oral, mouse: LD50 = 15 mg/kg. In large doses it is a powerful
poison, causing unconsciousness, delirium, convulsions, gastro-
enteritis, and stimulation of the respiratory center followed by
paralysis, from which death sometimes results.

29. Assignment-612
Thank you !