Antagonizing effects of YM-14673, a new TRH derivative, on behavioral and electroencephalographic changes in reserpinized animals.
Effects of YM-14673 (N alpha-[[S)-4-oxo-2-azetidinyl)-carbonyl]-L-histidyl-L-prolinamide dihydrate), a new TRH derivative, on reserpine-induced behavioural and electroencephalographic changes were observed in comparison with those of TRH. YM-14673 antagonized reserpine-induced hypothermia and decrease in convulsion threshold in mice. The number of PGO waves recorded from the lateral geniculate body was decreased by administration of YM-14673 in reserpinized cats. The anti-reserpine activity of intravenous YM-14673 was about 8-20 times more potent than that of TRH. In inhibiting reserpine-induced hypothermia, the oral ED2 degrees C relative to IV ED2 degrees C as an indirect indication of absorption rate of the drugs was 15 for both YM-14673 and TRH. These results suggest that YM-14673 possesses more potent facilitatory effects on the central monoamine systems than TRH.
D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D002415:Cats; D004151:Dipeptides / Q000494:pharmacology*; D004569:Electroencephalography; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012110:Reserpine / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
D001384:Azetidines; D001385:Azetines; D004151:Dipeptides; D013973:Thyrotropin-Releasing Hormone; C054995:azetirelin; D012110:Reserpine