RT Journal Article
SR Electronic
T1 COMPARATIVE ASSAY OF ANTIEPILEPTIC DRUGS BY "PSYCHOMOTOR" SEIZURE TEST AND MINIMAL ELECTROSHOCK THRESHOLD TEST
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 273
OP 283
VO 107
IS 3
A1 W. C. Brown
A1 D. O. Schiffman
A1 E. A. Swinyard
A1 L. S. Goodman
YR 1953
UL http://jpet.aspetjournals.org/content/107/3/273.abstract
AB In order to determine whether the recently described experimental "psychomotor" seizure (PsM.) test in animals is a useful laboratory procedure for the screening and assay of potentially valuable agents in psychomotor epilepsy and to ascertain whether the assay results differ from those obtained by means of the minimal electroshock threshold (M.E.T.) test, eight clinically useful antiepileptic drugs have been examined for anticonvulsant potency by these two electroshock threshold tests. On the basis of the results obtained, the following conclusions are reached: (1) All the drugs tested are more potent by the M.E.T. than by the PsM. test, with the exception of Tridione, the effective doses of which are not significantly different. It is thus more difficult to prevent experimental "psychomotor" seizures with drugs than to elevate the threshold for minimal electroshock seizures. However, the difference in ED50s by the two tests largely disappears when the current intensity employed in the PsM. test is reduced from 4 times threshold to two times threshold. (2) Phenobarbital is the most potent and Tridione the least potent compound by both tests. Paradione, Mesantoin, Mebaral and Phenurone are intermediate in potency between phenobarbital and Tridione. Dilantin and Thiantoin are ineffective by both tests. (3) The comparative potency rankings of the 8 drugs by the two tests show remarkable similarity. (4) No correlation between potency ranking of a drug by the PsM. test and its clinical value in psychic seizures can be discerned. Indeed, drugs ineffective in psychomotor epilepsy rank higher than does Phenurone, an agent acknowledged to be superior in the management of this disorder. (5) The protective index (P.I.) of Phenurone based on the PsM. tests is the only P.I. value which is greater than 1.0, but various data and reasons are presented which necessitate the conclusion that this high P.I. value may be without special significance and that the PsM. test does not reveal anti-psychomotor specificity of anticonvulsant drugs. Attention has been called to those properties of the PsM. seizure (including safety factor of stimulating current) which constitute advantages of the PsM. over the M.E.T. test as a measure of the effects of anticonvulsant drugs on seizure threshold; the possibility of the routine use of the PsM. test is discussed. The lack of specificity of the PsM. seizure for the detection of clinically useful antipsychomotor agents in no way detracts from its value as a tool for the study of various other properties of anticonvulsant drugs. Caution is again urged in the interpretation of antiepileptic drug assay data obtained in animals, since all currently employed laboratory tests have definite limitations in their predictive value for antiepileptic drug potency and specificity in various types of clinical seizures.