Screening Method Of Anti-Epileptic
Content
• Introduction
• Symptoms of epilepsy
• Classification of seizure
• Pathophysiology of epilepsy
• Selection of Anti-epileptic drug
• Preclinical evaluation
• In vitro method
• In vivo method
Introduction
• Epilepsy is a very commaon disorder characterised by
seizures, which take various forms and result from
neurongal discharges, with or without characteristic body
movement.
• Epilepsy derived from Greek - epilepsia - “taking hold of”
• Characterized by two or more unprovoked seizures.
• Epilepsy was described by JH Jackson.
Symptom
• Seizure symptoms vary depending on the type of seizure.
Because epilepsy is caused by certain activity in the
brain, seizures can affect any brain process. Seizure
symptoms may include:
• Temporary confusion.
• A staring spell.
• Stiff muscles.
• Uncontrollable jerking movements of the arms and legs.
• Loss of consciousness or awareness.
• Psychological symptoms such as fear, anxiety
Classification of Seizures
Primary Genralised Partial Seizure Unclassifed Seizure
Tonic-Clonic seizure Simple partial seizure Infantile spasms
Absence seizure Complex partial seizure
Atonic seizure Partial seizure
Myoclonic seizure
Generalised seizure
• Whole brain invoved
• Characterised by immediate loss of
consicousness
• Type of genralised seizure
1.Tonic-clonic seizure(grand mal epilepsy):-
Cry - Unconsciousness - strong contraction of
all body muscles - clonic jerking - prolonged
sleep
1-2 min
Absence Seizure(Petit Mal Epilepsy)
• Prevalant in childern.
• Momemtary loss of
consciousnees
• Patient freezes & stares in
one direction
• No muscular movement &
jerking
• 1/2 mins
Atonic seizure
• Due to excessive
inhabitory discharge
• Relaxation & patient fall.
• Atonic seizures are a type
of seizure that causes
sudden loss of muscle
strength. These seizures
are also called akinetic
seizures, drop attacks or
drop seizures.
Partial Seizure
• Discharge begins locally,
remain localised.
• Symptoms depend on the
brain egion involved.
• Also known as
Psychomotor epilepsy.
Simple partial seizure (Focal epilepsy)
• Involvement of area of
cotex causes convulsions.
• No loss of consciousness.
• 1/2 to 1 min.
• Focal seizures are a type
of seizure that affects only
one side of your brain and
body
Complex partial seizure
• Attack of bizarre
purposeless movement.
• Impairment of
consciousness.
• 1-2 min.
Pathophysiology Of Epilepsy
• Seizures develop due to an imbalance between inhibitory
and excitatory signals in the brain.
• A seizure may initiate due to high-frequency bursts of
excitatory action potentials in neurons. This leads to
synchronous, hyperexcitable activity within a neuronal
population.
• In epilepsy, acquired or genetic factors effect the balance
between inhibitory (i.e. gabanergic) and excitatory (i.e.
glutamatergic) signals.
• Gabanergic: inhibitory, characterised by gamma-
aminobutyric acid (GABA) receptors. Ligand-gated ion
channel that allows flow of chloride ions. GABA is the
main inhibitory neurotransmitter that binds to these
receptors.
• Glutamatergic: excitatory, characterised by glutamate
receptors (multiple types: ion-channels and G-coupled
protein). Glutamate is a small neurotransmitter that can
active these receptors.
Selection of Anti-epileptic Drug
Primary GTC Partial Absence Atypical,Myoclonic
Valpraote Carbamazepine Valpraote Valporate
Lamotrigine Phenytoin Ethosuximide Toprimate
Toprimate Valpraote
PRECLINICAL EVALUATION
Animal Models of Seizure
• The usual approach to anticonvulsant drug testing in
animal is to observe effect of prior drug administration on
seizure produced by
• 1. Electrical stimulation of brain
• 2. Systemic adminidtration of a convulsant drug
• 3. Animal strains with spontaneous or sensory-evoked
convulsions
In Vitro methods
• Hippocampal slices
• Electrical recording from isolated brain cells
• GABA uptake in rat cerebral cotex
• TBPS binding assay
Method(in vivo method)
• Electroshock seizure
1.Pentylenetetrazol(PTZ) induced seizure
2.Thershold models
3.Strychine-induced convulsions
4.Isoniazid-induced convulsions
Theshold Models
Aim- Used to screen drug with efficacy against generalized
tonic clonic and focal seizure.
Requriment- Animal required- Mice (18-30gm)
Equipment required- Electrical Stimulator
Procedure- Animal section
Experimental grouping(Divided in to animal in to different
group)
Acclimation
Baseline measurement(Record under study before any
interventions)
Intervetion
Data collection
Threshold model(analyze the critical point)
Report and publication
Pentyleneterazole Induce Convulsion
Aim- To evaluate antiepileptic drugs. Pentylenetetrazole is
a CNS Stimulant. It produces jerky type of clonic convulsion
in rats and mice similar to petit mal type of convulsion in
man.
It causes direct depolarization of central neuron.
Also interfere with GABAergic inhibition.
Procedure- Two group of 10 Albino Swiss mice of either
sex (20-25gm).
• First group is injected with Diazepam 4mg/kg(i.p.).
• Second group as control.
• 30min after Diazepam treatment inject with 75 mg/kg of PTZ
by s.c.
• Each animal is observed for 1hr. in plastic cage.
• Seizure & myclonic convulsion are recorded.
• At least 80% of animal in control have to show convulsion.
Evaluation- The number of protected animal in treated group is
calculated as percentage of affected animal in control group.
• ED 50 value calculated & time interval between PTZ injection
and occurance of seizure can be meaured.
Isoniazid Induce Convulsion
Aim- Isoniazid is regarded as GABA synthesis inhibitor. it is
known to purpose convulsion in patient having history of
seizure.
Procedure- Two group each of 10 albino mice (18-22gm)
• First group is injected with Diazepam 5mg/kg(i.p.)
• Second group as control receive vehicle saline 10ml/kg
• 15min after s.c. injection/30 min after i.p./60 min after oral
route 300 mg/kg of INH injected by s.c. to the both group.
• During next 120 min clonic seizure tonic seizure and death is
recorded.
• At leat 80% of animal in control have to show convlsion.
Evaluation:-
• The percentage of seizure or death occuring in the control
group is taken as 100%.
• The supression of these effects in the treated groups is
calculated as percentage of control.ED 50 values are
calculated.
