PHARMACOLOGICAL STUDIES ON THE NOVEL ANTIALLERGIC AGENT HSR-609 - ITSEFFECTS ON BEHAVIOR IN MICE AND ELECTROENCEPHALOGRAMS IN RABBITS

We studied the central nervous system (CNS) effects of HSR-609 (3-[4-( 8-fluora-5,11-dihydrobenz[b]oxepino [4,3-b]pyridin-11-ylidene)piperidi no]propionic acid dihydrate), a novel amphoteric antiallergic agent ha ving antihistaminic activity. Its effects on the behavior of mice and the electroencephalograms (EEG) of unanesthetized and unrestrained rab bits after oral administration were compared with those of typical ant iallergic agents and the non-amphoteric basic compound PY-608 5,11-dih ydro-11-(1-methyl-4-piperidylidene)benz[b] oxepino [4,3-b] pyridine), which has a chemical structure similar to that of HSR-609. HSR-609 (3- 300 mg/kg) had no effect on general behavior, spontaneous locomotor ac tivity, hexobarbital-induced sleeping time and reserpine-induced hypot hermia in mice. HSR-609 (10-100 mg/kg) and terfenadine (100 mg/kg) had no effect on spontaneous EEG, sleep-wakefulness cycles and EEG power spectra in rabbits. On the other hand, cyproheptadine (3-30 mg/kg), ke totifen (30-100 mg/kg) and PY-608 (0.3-100 mg/kg) caused increases and /or decreases of spontaneous locomotor activity, prolongation of hexob arbital-induced sleeping time and antagonistic effects on reserpine-in duced hypothermia in mice. These agents (30 mg/kg) increased slow wave sleep and enhanced EEG power spectra at low frequency bands such as d elta and theta in rabbits. These findings suggest that HSR-609 has no inhibitory effect on the CNS due to its amphoteric chemical structure.