This document discusses experimental methods used to evaluate antiepileptic drugs. It describes two main methods - the electroconvulsion method and chemically induced convulsion method. The electroconvulsion method uses maximum electroshock seizures to induce tonic hind limb extension in rats and mice, mimicking grand mal epilepsy. The chemically induced convulsion method uses substances like leptazole to induce seizures that can be prevented by anticonvulsants, mimicking petit mal epilepsy. The document provides details on procedures, measurements, and results for both methods.

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2. Introduction
• A Seizure (from the Latin
• is a paroxysmal event due to abnormal, excessive,
hyper synchronous discharges from an aggregate of
central nervous system (CNS) neurons.
• Epilepsy describes a condition in which a person has
seizures due to a chronic, underlying process.
• Incidence ~0.3–0.5%
• Prevalence 5–10 persons per 1000.
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3. Historical Aspects
• Over the centuries the epilepsy is known as “the
falling sickness”, “the sacred disease”, “St. Johns
disease”.
• Among the famous who suffered from epilepsy
were Julius Caeser, Alexander the great &
Napolean Bonapart.
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4. • Hippocrates was the first person to dispel the
myth of epilepsy, as not being caused by devils
and spirits.
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5. • John Jackson:
.
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6. Classification Of Seizures
A) Partial
• Simple
• Complex
• Secondary generalized
B) Primary Generalized
• Absence
• Tonic-clonic
• Tonic
• Myoclonic
C) Unclassified
• Neonatal
• Infantile Spasms
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7. Experimental methods for evaluating
antiepileptic drugs
1)Electroconvulsion method.
2)Chemically induced convulsion method
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8. In vitro models
• Hippocampal slices model
• Electric recording from isolated brain cells
• GABA receptor binding assays
• Exitatory aminoacid receptor binding assays
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9. Disadvantages of in vitro study
• Serve as initial screening for drug discovery
• Not give proper idea about pharmacokinetics
and pharmacodynamics or PK-PD interaction
of compound in living animals.
• Not possible to study compensatory changes
that occur in body when drug is given.
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10. Electroconvulsion method:
• 1)Maximum Electroshock
Seizures(M.E.S.)
• Model of grand mal epilepsy
• End point : Tonic Hind Limb Extension
• The agents screened through this model considered
an antiepileptic drugs if it corrects or suppresses
Tonic Hind Limb Extension
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11. • Maximum current of such voltage is applied as to induce
convulsions in all the tested animals (rats, mice).
• A well characterized course of convulsion,
• (a short latent period, followed by a tonic extensor tonus
and then by a phase of clonic convulsion)
• The drugs effective in the test alter the seizure pattern by
suppressing the tonic phase of convulsions. Such drugs are
potentially useful in Grand mal epilepsy(Generalized Tonic
Clonic Seizures)
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12. • Materials and methods:
• Animal :Rat /Mouse
: 150-250 gm
• Drugs :Phenytoin (20-30mg/kg,i.p./po) ,
: Phenobarbitone sodium, 15 mg/kg i.p.
:Diazepam (3-4mg/kg i.p.)
• Instrument:
• Electro convulsiometer:
• Rat:150 mA ,50 Hz for 0.2 sec
• Mouse:12 mA ,50 Hz for 0.2 sec
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13. convulsiometer
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15. Tonic Hind Limb Extension
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16. • Methods:
• Step 1:
• Weight the animals and mark properly
• Divide animals into 3 group
• They are given stimulus with ear electrode.
• Phases of convulsions are recorded in each mouse
• The drugs are injected
• Step 2:
• Group 1: Isotonic saline
• Group 2: Phenytoin sodium, 30 mg/kg i.p.
• Group 3: Phenobarbitone sodium, 15 mg/kg i.p.
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17. • After 1 hour animals are given electroconvulsions
• Observations are noted
• Record whether ‘THLE’ Present /Absent
• Step 3:
• Observe the animal after MES
• Calculate percentage protection
• Percentage protection =No. of animals with THLE
absent /total no. animal ×100
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18. M.E.S.(Maximum Electroshock Seizure)
Group no Latent period (sec) Extensor tonus(sec) Clonic
convulsions(sec)
Before After Before After Before After
A 1 2 3 8 8 10 10
A 2 2 3 8 10 10 12
B 1 2 2 8 ------- 10 11
B 2 3 3 12 -------- 10 12
C 1 3 3 8 -------- 10 10
C 2 3 3 12 -------- 14 12
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19. Minimal Electroshock seizure Threshold: (MET)
• Measurement of minimal strength of current
required to elicit electroconvulsion.
2) Hyponatremic Electroshock seizure Threshold
(HET)
• animals injected with isomolar glucose solution
(10 ml/100 gm body wt.).
• This induces hyponatremia and lowers the M.E.T.
• Drugs elevate the threshold used in grandmal
epilepsy .
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20. 3) Psychomotor Seizures
• Mice are subjected to unidirectional current
pulses
• animal becomes stunned and shows
automatism lasting for 15-20 sec.
• Drugs inhibiting the effect of current in this
test are potentially useful in Psychomotor
seizures.
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21. 4) Kindling model of epilepsy:
A model for human focal epilepsy is that produced
in animals by “kindling”.
This consists of delivery of brief localized trains of
electrical stimuli to an area of the brain,
repeatedly, at about 24 hour intervals.
After a time, generalized motor seizures are
regularly elicited during such electrical
stimulation.
Useful in partial simple/complex seizure
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22. Chemically induced convulsion:
• A threshold dose of a suitable convulsant (e.g.
Leptazole, Strychnine) is injected in mice or
rats.
• This induces clonic type of convulsions.
• Some of the anticonvulsants (ethosuccimide,
sodium valproate) prevent these convulsions.
Such drugs may be potentially useful in
Petitmal epilepsy (Absence Seizures).
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23. (B) Chemical method:-
• Two mice (D1, D2) are selected.
• One is injected with antiepileptic drug
(sodium valproate) and
• other is kept as control.
• Then both mice are injected with leptazole
and observations are noted.
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24. Chemical method:
Convulsant Antiepileptic No. of animal
showing
convulsions
No. of animals
showing protection
from convulsions
Drug and dose Drug and dose
Leptazole
(70 mg/kg i.p)
Normal Saline 1 nil
Leptazole
(70 mg/kg i.p)
Sodium Valporate
40 mg/kg i.p.
nil 1
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25. Assignment
a) Define epilepsy.
b) Classify epilepsy.
c) Enumerate experimental methods for
evaluation of anticonvulsant.
d) Enlist one drug of choice each for common
type of epilepsy.
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26. Selection Of Anti-epileptic Drug
• Primary GTC: Phenytoin
• Partial: Carbamazepine
• Absence: Ethosuxamide
• Myoclonic seizure: Valporic acid
• Drug resistant seizures: Lamotrigine
• Febrile convulsions: Diazepam
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27. Classification Of Seizures
A) Partial
• Simple
• Complex
• Secondary generalized
B) Primary Generalized
• Absence
• Tonic-clonic
• Tonic
• Myoclonic
C) Unclassified
• Neonatal
• Infantile Spasms
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