Central excitatory actions of flurazepam

Abstract

Toxic actions of flurazepam (FZP) were studied in cats, mice and rats. High doses caused an apparent central excitation, most clearly seen as clonic convulsions, superimposed on general depression. Following a lethal dose, death was always associated with convulsions. Comparing the relative sensitivity to central depression and excitation revealed that rats were least likely to have convulsions at doses that did not first cause loss of consciousness, while cats most clearly showed marked central excitatory actions. Signs of FZP toxicity in cats included excessive salivation, extreme apprehensive behavior, retching, muscle tremors and convulsions. An interaction between FZP and pentylenetetrazol (PTZ) was shown by pretreating mice with FZP before PTZ challenge. As a function of dose, FZP first protected against convulsions and death. At higher doses, however, convulsions again emerged. These doses of FZP were lower than those that would alone cause convulsions. These results may be relevant to the use of FZP in clinical situations in which there is increased neural excitability, such as epilepsy or sedative-hypnotic drug withdrawal.