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  • Title: Central nervous system effects of the novel antiallergic agent HSR-609 and typical antiallergic agents using behavioral and electroencephalographic analyses in dogs.
    Author: Kakiuchi M, Ohashi T, Tanaka K, Ohara N, Kamiyama K, Morikawa K, Kato H.
    Journal: Nihon Shinkei Seishin Yakurigaku Zasshi; 1998 Oct; 18(5):189-99. PubMed ID: 10028490.
    Abstract:
    We studied the central nervous system (CNS) effects of 3-[4-(8-fluoro-5, 11-dihydrobenz[b] oxepino[4, 3-b]pyridin-11-ylidene)piperidino]propionic acid dihydrate (HSR-609), a novel amphoteric antiallergic agent having antihistaminic activity. Its effects on gross behavior, spontaneous electroencephalograms (EEG) and some pharmacological parameters of unanesthetized, unrestrained dogs with chronic indwelling brain electrodes after oral administration were compared with typical antiallergic agents and 8-fluoro-5, 11-dihydro-11-(1-methyl-4-piperidylidene)benz[b] oxepino[4,3-b]pyridine (PY-608), a non-amphoteric basic compound having a similar chemical structure to HSR-609. HSR-609 (1, 10 and 100 mg/kg) and terfenadine (100 mg/kg) had no effect on the behavior, EEG patterns, sleep-wakefulness cycles or EEG power spectrum. Cyproheptadine (10 mg/kg), ketotifen (30 mg/kg) and PY-608 (10 mg/kg) increased slow waves with high amplitude in all EEG leads and caused dissociation between the slowing of EEG and waking behavior. Both azelastine (30 mg/kg) and oxatomide (100 mg/kg) caused generalized seizure discharges accompanied by agitation with the former and sedation with the latter. These findings suggest that observations of behavior and EEG in conscious dogs can be useful for clarifying the pharmacological characteristics of various antiallergic agents on the CNS. We were able to show that HSR-609 has no effect on the behavior and EEG of dogs because of its amphoteric chemical structure.
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