Anticonvulsive properties of YM-14673, a new TRH analogue, in amygdaloid-kindled rats.
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 less than 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.
Yatsugi
S
S
Medicinal Research Laboratories I, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki Pref., Japan.
Yamamoto
M
M
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants; D001384:Azetidines / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000927:Anticonvulsants; D001384:Azetidines; D004151:Dipeptides; C054995:azetirelin