CORRELATION BETWEEN ANTICONVULSANT ACTIVITY AND PLASMA CONCENTRATION OF BROMIDE

¹ Departments of Pharmacology, University of Utah College of Medicine and College of Pharmacy, Salt Lake City, Utah

The anticonvulsant potencies (ED₅₀s) of sodium bromide were determined in mice by a battery of six assay procedures. In addition, the dose which produced evidence of minimal neurological deficit in 50 per cent of animals (TD₅₀) was determined and protective indices (P.I. = TD₅₀/ED₅₀) were calculated. The concentrations of plasma bromide attained after administration of the TD₅₀ and each ED₅₀ were also measured. The results are as follows:

1 . The TD₅₀ of sodium bromide, determined in mice 5 hours after intraperitoneal administration, is 2125 mgm./kgm.

2. Sodium bromide is effective by all anticonvulsant tests employed and modifies seizure pattern as well as elevates seizure threshold. It is most potent when tested for ability to modify the pattern of maximal seizures induced by intravenous Metrazol, and to elevate the thresholds for seizures induced by Metrazol and by low frequency electrical stimulation with interrupted unidirectional pulses of short duration; the P.I.s derived from data obtained by these three tests are 1.70, 2.34 and 2.31, respectively. Bromide is least potent when tested for ability to modify the pattern of maximal seizures induced by supramaximal electroshock and to elevate the thresholds for minimal seizures induced by conventional electroshock in normal or hyponatremic (low-threshold) mice; the P.I.s derived from values obtained by these three tests are not significantly different from unity.

3. The concentrations of plasma bromide varied from 29 to 69 mEq./l. and, except for the concentration in hyponatremic mice, were linearly related to the log dose of sodium bromide. The lower concentration of plasma bromide in hyponatremic mice is the result of the movement of an appreciable amount of this ion into the extracellular reservoir established by the injection of isosmolar glucose solution into the peritoneal cavity.

These results re-emphasize the fact that current methods of laboratory assay as yet have only limited value for the prediction of clinical antiepileptic potency or of drug specificity for particular types of seizures.