Neuroleptic-induced seizures. An in vitro technique for assessing relative risk

To estimate the relative risk of various neuroleptic medications for patients with epilepsy or likely to have neuroleptic-induced seizures, their action on spike activity in perfused guinea pig hippocampal slices was studied. Within the range of concentrations studied, molindone hydrochloride, butaclamol hydrochloride, pimozide, and fluphenazine dihydrochloride produced the least increase in excitability. There were also differences in the dose-response curves. Chlorpromazine, thioridazine, and pimozide produced an inverted U-shaped curve. For haloperidol and fluphenazine, excitability tended to increase and them plateau. Molindone and butaclamol produced no increase in excitability. Combinations of neuroleptics had synergistic effects, while the anticonvulsant diazepam inhibited neuroleptic-induced excitability. This article discusses the clinical implications of these findings and their effect on theories of which neuroleptics might produce the fewest seizures.