Electroshock seizure test

The carbohydrate-based 1,3,2-dioxathiolane A, -dioxide 23 (Section 6.05.3.1) has demonstrated an exceptional anticonvulsant activity in the standard maximal electroshock seizure test. Compound 23 is much more potent than structural analogs, and approximately 8 times more potent than the isosteric topiramate <1998JME1315>. 

A ter el at. (1984) documented the anticonvulsant properties of PBO and compared them with those of clinically established anti epileptic drugs. PBO administered inlrapcritoncally to mice exerted peak anti maximal electroshock activity and peak neurotoxicity at 5 and 7 hours, respectively. The median neuroluxic dose was I.69U mg kg"1. In the maximal electroshock seizure test I he median effective dose (HD j) was 457 mg kg"1 and the protective index (PI) was 3,69. In the subcutaneous pentylenetetrazol (PTZ) test the ED u was 443 mg kg 1 and PI was 3.81. PBO prevented seizure spread and elevated seizure threshold, and its PI compared favourably with those of clinically useful anticonvulsants,... 

The maximal electroshock seizure (MES) test was used to show efficacy of antiepileptic agents against partial and generalized seizure type epilepsy among therapy-resistant epileptic patients. 

In animals, the profile of antiseizure properties for CBZ is similar to that of phenytoin. CBZ is effective in the maximal electroshock (MES) test (electrically induced seizure test) but is ineffective against pentylenetetrazole-induced seizures. It is not effective for absence or myoclonic seizures and, indeed, may exacerbate their onset (30,41). Like phenytoin, CBZ acts on voltage-dependent sodium channels to prevent the spread of seizures. CBZ depresses synaptic transmission in the reticular activating system, thalamus, and limbic structures. In a double-blind, crossover study in patients whose seizures were not controlled completely by combinations of AED, CBZ was equal in efficacy to phenobarbital and phenytoin in controlling seizure frequency, and side effects were minimal. 

It has become clear that drugs which are effective in protecting mice against PTZ are effective in absence seizures while those able to control the tonic response to maximal electroshock are effective in tonic-clonic seizure. Some drugs are effective in only one test and clinical condition whilst a few are active in both (Table 16.1). Experimental focal seizures are indicative of partial seizures. 

The preclinical investigation of a newly proposed antiepileptic in experimental animals typically involves the use of electrical stimulation (electroshock) to induce maximal generalized seizures (MES), and the systemic administration of convulsant drugs (e.g., pentylenetetrazole) to elicit minimal seizures. The use of animals genetically susceptible to seizures caused by light or specific noise is also prevalent [175]. The efficacy of the antiepileptic is then tested against the seizures induced. (For leading references see [175].)... 

A number of animal models are currently available for anticonvulsant screening [13,14]. Two basic models used are Maximal Electroshock Test (MEST) and Subcutaneous Pentylenetetrazole Seizure Threshold Test (ScMET). Anticonvulsant activity in MEST predicts the ability of the testing material or compound in preventing the spread of seizure discharge and effectiveness in the treatment of grandmal seizures, while activity in ScMET predicts the ability to elevate seizure threshold and effectiveness in myoclonic seizures. 

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