Abstract
The patterns of maximal seizures evoked in mice by the intravenous injection of 38 mgm./kgm. Metrazol and by supramaximal electroshock have been compared. In addition, eight clinically useful antiepileptic drugs were tested for their ability to prevent the characteristic hindleg tonic extensor component of maximal Metrazol seizures (M.M.S.) and maximal electroshock seizures (M.E.S.). The results were as follows:
(1) The M.M.S. and M.E.S. patterns in mice are similar in that the major feature is a tonic convulsion characterized by initial flexion and subsequent extension of the hindlegs; the duration of the tonic components of the two types of seizures is remarkably similar. However, there are important differences in the M.M.S. and M.E.S. The M.M.S. is clonic-tonic whereas the M.E.S. is tonic-clonic. Postictal relaxation supervenes after the tonic component of the M.M.S. whereas a clonic component of long duration follows the tonic component of the M.E.S. Recurrent seizures frequently occur after intravenous Metrazol, but are never observed after supramaximal electroshock of brief duration. The mortality rate from M.M.S. is about ten times higher than that from M.E.S. Explanations have been advanced for these similarities and differences in the two types of seizure pattern.
(2) Tridione, Paradione, phenobarbital, Mebaral and Phenurone are much more potent in modifying M.M.S. than M.E.S.; in sharp contrast, the three hydantoin derivatives—Dilantin, Mesantoin and Thiantoin—are much more potent in modifying M.E.S. than M.M.S. A probable explanation for the division of the drugs into these two classes is found in the fact that the hydantoin derivatives excel in the inhibition of seizure spread but are relatively ineffective in elevating seizure threshold; in contrast, all the other drugs tested possess both mechanisms of anticonvulsant action. Inhibition of seizure spread is probably paramount for the drug-induced modification of M.E.S. whereas a large component of chemoshock threshold elevation is important for the drug-induced modification of M.M.S.
Certain features of the maximal seizure and its sequelae are dependent on the nature of the stimulus initiating the convulsion; however, the tonic extensor component is constant in its character and time course and is independent of the stimulus evoking it. The M.M.S. test is not suitable as a routine anticonvulsant assay procedure, but a study of its properties has contributed to the understanding of maximal seizures and of the mechanism and the spectrum of action of anticonvulsant drugs.
Footnotes
- Received January 9, 1953.
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