slide on screening of convulsion

1. Anti convulsant
PRESENTED By-
Kumari Swarupma
Pharmacology
M.pharma
Submitted to-
DR.Sandipan Dasgupta
(GUIDE)
NSHM KNOWLEDGE
CAMPUS KOLKATA

2. INTRODUCTION-
Anticonvulsants (also commonly known as antiepileptic
drugs or as antiseizure drugs) are a diverse group
of pharmacological agents used in the treatment
of epileptic seizures.
Anticonvulsants are also increasingly being used in the treatment
of bipolar disorder and borderline personality disorder.
Epilepsy is a group of disorders of the CNS characterised by
proximal cerebral dysrhythmia, manifestation as brief
episode(seizures)of loss or disturbance of consciousness, with
or without characteristic body movement(convulsion),sensory
or psychiatric phenomena.
It is a very common disorder, characterised by seizures.

3. SEIZURE TYPE FEATURES CONVENTIONAL
ANTISEIZURE
DRUGS
RECENTLY
DEVELOPED
ANTISEIZURE
DRUGS
1.Partial
seizures
a)Simple partial Diverse
manifestations
determined by the
region of cortex
activated by the
seizurelasting.Its last
for
20 to 60 sec.Key
feature is
preservation
Carbamazepine,
phenytoin,
valproate
Gabapentin,
lamotrigine,
levetiracetam,
tiagabine,
topiramate,
zonisamide
b)Complex
partial
Impaired
consciousness lasting
30sec to 2min,often
Carbamazepine,
phenytoin,
valproate
Gabapentin,
lamotrigine,
levetiracetam,
Classification

4. 2.Generalized
seizures:
a)Absence
seizure
Abrupt onset of
impaired
consciousness
associated with
staring & cessation
of ongoing activities
typically lasting
less than 30 sec
Ethosuximide,
valproate
Lamotrigine
b)Myoclonic
seizure
A brief (perhaps a
sec), shock like
contraction of
muscles which may
be restricted to part
of one extremity or
may be generalized
Valproate Lamotrigine,
topiramate
c)Tonic-clonic
seizure
It is not preceded by
a partial seizure
Carbamazepine,
phenobarbital,
phenytoin,
primidone,valproat
e
Lamotrigine,
topiramate

5. PRECLINICAL
EVALUATION
5

6. ANIMAL MODELS OF SEIZURE
 The animal model are essential in the pre-clinical research of
new drugs to develop new treatment approaches for epileptic
seizures.
 The drug effect chosen for the study can be assessed on
following parameters:
i. Change in the threshold,
ii. A qualitative change in pattern of the motor
seizure,
iii. Changes in the EEG pattern,
iv. Change in incidence of seizures.

7. ANIMAL MODEL OF SEIZURE
Animal Model of Seizure
Genetic rat model
of epilepsy
Electroshock
seizure
Chemical
induced model
Kindled rat
seizure model
Chemical
induced model
Pentylenetetrazol
(PTZ) induced
seizure
Strychnine
induced seizure
Picrotoxin induced
seizure
Isoniazid induced
seizure
Bicuculine
induced seizure

8. 1.Electroshock Seizures In Mice & Rats
 Protection against electroshock induced seizures in mice and rats
is used as an indication for compounds which may prove effective
in
 Electric stimuli evoke tonic hind limb extensions, which are
suppressed by anti-epileptic drugs.
Types of electroshock seizures
Supramaximal Electroshock.
 Extensor Seizure Latency.
 Psychomotor Electroshock.
 Minimal Electroshock Threshold.

9. Procedure :-
Tonic clonic convulsions are produced in mice or rats.Through
high electroshock currents by placing electrodes on the ears.
Purpose- induce the most intense physiologically possible seizure by
a method analogous to human electroshock therapy.
Current used:
oRat : 150mA
oMice : 50 mA 0.2 second duration

10. Chemical induced seizures :
i)Pentylenetetrazol(PTZ)induced seizures
Purpose : Pentylenetetrazole Produces convulsion similar to
petitmal type of convulsion in rats and mice.
Procedure:
FIRST GROUP SECOND GROUP
INJECTED-Diazepam
4mg/kg(i.p)
control
 Two groups of 10 Albino Swiss mice of either sex (20-25 gm)
 30min after Diazepam treatment inject with 75 mg/kg of PTZ by s.c.
 Each animal is observed for 1 hr. in plastic cage

11. II)ISONIAZID INDUCED CONVULSIONS
Purpose :
 Isoniazid is a GABA synthesis inhibitor.
 It produce convulsions in patients having history of seizures.
Procedure:
o Two groups each of 10 albino mice (18-22gm)
o 15 min after s.c. injection/30min after i.p./60 min after oral route, 300 mg/kg
of INH is injected by s.c. to the both groups.
o During next 120 minutes clonic seizure, tonic seizure and death is recorded.
Parameter to be Evaluate:
 Status of animal after 30 minutes.
 Status of animal after 24 hour.
 Percentage protection
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FIRST GROUP SECOND GROUP
INJECTED-Diazepam 5mg/kg. (i.p.) as control, receive saline.

12. III)PICROTOXINE INDUCED CONVULSIONS
Purpose : Picrotoxin is regarded as GABAA-Antagonist modifying the
function of chloride ion channel of GABAA receptor complex.
Procedure:
 Two groups of 10 Albino mice of either sex (18-20 gm)
 First group is treated with 5mg/kg Diazepam i.p.
 Second group is treated with normal saline, as control group
 15mins after i.p. inject 3.5 mg/kg of Picrotoxin through i.p. route
 Observe the symptoms during next 30 min.
Parameter to be Evaluate:
 Status of animal after 30 minutes.
 Status of animal after 24 hour.
 Percentage protection
12

13. IV)STRYCHNINE INDUCED CONVULSIONS
Purpose:
 The convulsive action of strychnine is due to interference with post
synaptic inhibition mediated by glycine.
 Strychnine act as selective and competitive antagonist to block
inhibitory effect of glycine to all glycine receptors.
Procedure:
 Two groups of 10 Albino mice of either sex (18-20 gm)
 First group receive 5mg/kg Diazepam i.p.
 Second group is control, receive normal saline.
 One hour later, mice are injected with 2mg/kg strychnine (i.p.)
 Observe the symptoms during next 30 min.
Parameter to be Evaluate:
 Status of animal after 30 minutes.
 Status of animal after 24 hour.
 Percentage protection
13

14. VI)BICUCULINE TESTS IN RATS
Purpose : Bicuculine antagonize the action of GABA by competition on
postsynaptic receptor and induces Myoclonic Seizure.
Procedure:
 Two groups of 10 Albino mice of either sex (18-20 gm)
 First group is treated with 5mg/kg Diazepam i.p.
 Second group is treated with normal saline, as control group
 15mins after i.p. inject 1 mg/kg of Bicuculine through i.v. route
 Observe the symptoms during next 30 min.
Parameter to be Evaluate:
 Status of animal after 30 minutes.
 Status of animal after 24 hour.
 Percentage protection

15. STATUS EPILEPTICUS
Different animal models used are:
 pilocarpine induced status epilepticus.
 Lithium pilocarpine induced status epilepticus.
 Lithium methomyl induced seizure in rats.
 Electrical stimulation of hippocampal perforant pathways.
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16. CHEMICAL INDUCED STATUS EPILEPTICUS
 Pilocarpine
 Cholinomimetic
 Can produce status epilepticus in rats
 Dose : 380-400 mg/kg
 Route : ip
 Lithium- Pilocarpine;
 Pretreatment with lithium – 3meq/kg ip
 Followed by pilocarpine – 30-40 mg/kg ip
 Lithium – methomyl
 Pretreatment with lithium
 Methomyl – 5.2mg / kg s.c.
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17. GENETIC ANIMAL MODEL FOR EPILEPSY
Totterer Mice:
 Homozygous strain totterer mice are prone to spontaneous
epileptic seizure
 Broad based ataxic gate
 By 3 to 4 weeks of age → develop frequent partial seizure
 Spontaneous focal motor seizure occur a few times a day →
unilateral clonic jerk of limbs with secondary generalization
 Also exhibit absence seizure with synchronous 6-7 per second
spike wave discharges in EEG
 Two seizure type in one model
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18. CONCLUSION
 Ideal model of epilepsy should show the following characteristics
 Development of spontaneously occurring seizures
 Type of seizure similar to that seen in human epilepsy
 EEG correlates of epileptic –like activity
 Age dependency in the onset of epilepsy as seen in many
epileptic syndromes
 At present no model follows all criteria
 Only genetic model come close
 The antiepileptic drug development program primarily based
on two seizure model, the MES and the PTZ.
 Single method of screening of antiepileptic drugs can not predict
the full pharmacological profile of the drug.
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19. Reference:
1.Experiment modeling of anxiety.(by- Nimish L.Pathak,Sanjay
B.Kasture,Nayna M.Bhatt and Ritesh
G.Patel)www.japsonline.com
2.Manual of pharmacology and therapeutics-Goodman & Gilman's
3.Drug discovery and evaluation(pharmacological assays-2nd
edition)-H.Gerhard Vogel
4.S. K. Kulkarni, Handbook of Experimental Pharmacology.
5.S.K Gupta, text book of screening methods and toxicology, page no:401-
419
6.Tripathi KD, Essentials of medical pharmacology, 6th edition, chapter-7
page no:401-413
7.N S Parmar, screening methods of pharmacology, chapter-5 page no:90-
97