Quantitative electroencephalographic profile of 3-(4-hydroxy-1-piperidinyl)-6-(2,4-dichlorophenyl)-pyridazine (SR 41378) in the rat.

Abstract

Quantitative electroencephalographic (QEEG) analysis was performed in rats following the oral administration of SR 41378 [3-(4-hydroxy-1-piperidinyl)-6-(2,4-dichlorophenyl)-pyridazine], a novel aminopyridazine derivative, which has been shown to possess anticonvulsant, antianxiety and hypnotic activities in mice and rats. The EEG effects of SR 41378 (10, 30 and 100 mg/kg) were compared to those of secobarbital (30 and 60 mg/kg) and diazepam (1, 3 and 10 mg/kg). SR 41378 and secobarbital increased the power of the middle-frequencies (8-16 Hz) of the EEG, reduced that of 4-8 Hz (theta) activities and did not affect 1-4 Hz (delta) activities. Diazepam also increased the power of middle-frequency activities and decreased that of both delta and theta activities. Quantitative EEG profiles were calculated from the mean integrated power (MIP) of selected frequency bands. The QEEG profile of SR 41378 was found to share common characteristics with those of secobarbital and diazepam: dose-dependent decrease of theta band MIP and increase of 8-20 Hz (middle beta bands) MIP. However, both SR 41378 and secobarbital induced a reduction of the 28-32 Hz (fast beta bands) MIP, whereas diazepam diminished the delta band. These results suggest that SR 41378, a novel chemical structure, shares common psychotropic properties with barbiturates and benzodiazepines.