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We studied the central nervous system (CNS) effects of HSR-609 (3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11- ylidene) piperidino]propionic acid dihydrate), a novel amphoteric antiallergic agent having antihistaminic activity. Its effects on the behavior of mice and the electroencephalograms (EEG) of unanesthetized and unrestrained rabbits after oral administration were compared with those of typical antiallergic agents and the non-amphoteric basic compound PY-608 (8-fluoro-5,11-dihydro-11-(1-methyl-4-piperidylidene)benz [b]oxepino[4,3-b]pyridine), which has chemical structure similar to that of HSR-609. HSR-609 (3-300 mg/kg) had no effect on general behavior, spontaneous locomotor activity, hexobarbital-induced sleeping time and reserpine-induced hypothermia 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), ketotifen (30-100 mg/kg) and PY-608 (0.3-100 mg/kg) caused increases and/or decreases of spontaneous locomotor activity, prolongation of hexobarbital-induced sleeping time and antagonistic effects on reserpine-induced hypothermia in mice. These agents (30 mg/kg) increased slow wave sleep and enhanced EEG power spectra at low frequency bands such as delta and theta in rabbits. These findings suggest that HSR-609 has no inhibitory effect on the CNS due to its amphoteric chemical structure.

Pharmacological Studies on the Novel Antiallergic Agent HSR-609: Its Effects on Behavior in Mice and Electroencephalograms in Rabbits.