Pharmacological Studies on the Novel Antiallergic Agent HSR-609: Its Effects on Behavior in Mice and Electroencephalograms in Rabbits
Masato Kakiuchi, Tetsuo Ohashi, Kazuo Tanaka, Kazuko Kamiyama, Kouji
Morikawa and Hideo Kato
Research and Development Division, Hokuriku Seiyaku Co., Ltd., 37-1-I Inokuchi,
Katsuyama, Fukui 911, Japan
Abstract: 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 a 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.
Keywords: Antiallergic agent, Central nervous system effect, Behavior
(mouse), Electroencephalogram (rabbit), HSR-609