Naloxone epileptogenesis in monkeys

EW Snyder, RE Dustman and C Schlehuber

The electroencephalographic effects of a range of doses of naloxone were evaluated in an effort to address the apparent epileptogenic properties of the drug. Electrographic activity was recorded from epidural electrodes in eight monkeys. The records were visually inspected and subjected to power spectral analyses. Concurrent visual evoked potentials were recorded and analyzed by standard procedures. Large doses (greater than 32.0 mg/kg i.m.) of naloxone were quickly and reliably succeeded by high voltage electrographic seizure activity at cortex. Lower doses (greater than or equal to 8.0 mg/kg) were followed by increased voltage in high frequency electroencephalogram (EEG) and spiking activity. Visual evoked potential latencies were reliably extended. As determined by power spectral analyses and third order slope analyses, the drug effects on EEG were related to time and dose. The early effects of high doses mimicked the maximal effects of low doses. It is concluded that seizures which follow high doses (48.0-- 64.0 mg/kg) of naloxone are derived from changes which are evident after doses which approach those used clinically to antagonize opiates. Such changes are, however, not readily apparent under visual inspection of the EEG.

Volume 217, Issue 2, pp. 299-305, 05/01/1981
Copyright © 1981 by American Society for Pharmacology and Experimental Therapeutics