ANTICONVULSIVE PROPERTIES OF YM-14673, A NEW TRH ANALOG, IN AMYGDALOID-KINDLED RATS

被引:22
作者
YATSUGI, SI
YAMAMOTO, M
机构
[1] Medicinal Research Laboratories I, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Tsukuba City, Ibaraki Pref.
关键词
YM-14673; TRH; AMYGDALOID KINDLING; AFTERDISCHARGE; RAT;
D O I
10.1016/0091-3057(91)90031-V
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Effects of YM-14673 (N-alpha-[{(S)-4-oxo-2-azetidinyl}-carbonyl}-L-prolinamide dihydrate), a new TRH analogue, on the development of kindling and the duration of afterdischarge (AD) were observed in amygdaloid-kindled rats in comparison with those of TRH. The right medial amygdaloid nucleus was electrically stimulated once a day for establishment of kindling. YM-14673 and TRH were administered intraperitoneally 15 and 30 min prior to electrical stimulation from 2 days after the first stimulation, respectively, and the number of stimulations required for the development of generalized seizures was measured. YM-14673 (1 mg/kg) showed tendency to suppress the development of kindling (p < 0.1), but TRH even at high dose (10 mg/kg) showed little effect on it. In addition, the experiment for the AD duration was conducted in full-kindled rats from one day after at least 3 reproducible generalized seizures were elicited by electrical stimulation of the medial amygdaloid nucleus once a day. Both YM-14673 (1 mg/kg) and TRH (10 mg/kg) administered 15 and 30 min prior to electrical stimulation of the amygdala, respectively, significantly shortened the AD duration in full-kindled rats. At these doses, both drugs desynchronized spontaneous cortical electroencephalogram (EEG) in normal rats. These results indicate that YM-14673 seems to possess anticonvulsive property in rats.
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页码:669 / 672
页数:4
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