Screening of Anticonvulsant Drugs

Lab #5

Outlines
Brief overview on epilepsy
Anticonvulsant drugs
Methods of screening of

anticonvulsants

Epilepsy
Epilepsy: disorder of brain function characterized by a

periodic and unpredictable occurrence of seizures

Seizure: transient alteration of behavior due to

disordered and rhythmic firing of population of brain

neurons

Convulsion: The major motor manifestations of a

seizure (rhythmic jerking of the limbs)

Pathophysiology of Epilepsy
High frequency discharge of impulses by

interconnected cerebral neurons

Starts locally then spread
Enhancement of excitatory transmission
Reduction of inhibitory transmission

Causes of Epilepsy
Neurological diseases
Medical trauma as stroke
Infection
Head injury
Neoplasm of brain
Heredity

Types of Epilepsy
Partial (small area in brain, no loss of
consciousness)

Generalized (spread over larger area of brain,

e.g. tonic-clonic, absence seizure)

Status epilepticus (convulsions without

cessation)

Anticonvulsant Drugs
Drugs that enhance GABA action:
phenobarbital, benzodiazepines, vigabatrin,
tiagabine
Drugs that inhibit sodium channels
function: phenytoin, carbamazepine,
valproate, lamotrigine
Drugs that inhibit calcium channels
function: ethosuximide

Screening Methods For Anticonvulsants

Principle
The ability of anticonvulsant drug to
partially or completely antagonize
siezure induced either chemically or
electrically

Screening Methods For Anticonvulsants

Supramaximal electroshock: tonic-

clonic, mice, repetitive shocks (high

freq.) , diff. doses IP inj.
Psychomotor electroshock: low freq.,
absence, mice
Leptazol seizure method: mice, SQ
pentylentetrazol (100 mg/kg)

PD50
Protective dose 50: the dose that is

required to abolish seizure in 50% of

animal
Comparison of drug effectiveness

Screening Methods For Anticonvulsants

Strychnine-induced seizure: tonic

Picrotoxine-induced seizure: clonic

Tonic vs Clonic
Clonic convulsion

Tonic convulsion

-Produced by dose of

-Produced by dose of

medullary stimulants
-Asymmetric
-Coordinated
-Spontaneous
-Intermittent
-Removed by decapitation

spinal cord stimulants

-Symmetric
-Non-coordinated
-Reflex in origin
-Continuous
-Removed by pithing

Lab work
Drug injected

Strychnine Or
picrotoxine
25 mg/kg
phenobarb.
50 mg/kg
phenobarb.
75 mg/kg
phenobarb.

Onset of
convulsion

Number of
convulsion/1min

Chart