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)

PD 50  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 convulsionTonic convulsion - Produced by ↑dose of medullary stimulants - Asymmetric - Coordinated - Spontaneous - Intermittent - Removed by decapitation - Produced by ↑dose of spinal cord stimulants - Symmetric - Non-coordinated - Reflex in origin - Continuous - Removed by pithing

Lab work Drug injectedOnset of convulsionNumber of convulsion/1min Strychnine Or picrotoxine 25 mg/kg phenobarb. 50 mg/kg phenobarb. 75 mg/kg phenobarb.

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