Effects of thyrotropin releasing hormone and its analogues on unconsciousness following head injury in mice.
We examined the effects of thyrotropin releasing hormone (TRH) and its analogues (DN-1417: gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide citrate; MK-771: L-pyro-2-aminoadipyl-histidyl-thiazolidine-4-carboxamide; TSII-37: H-Lys-Gln-His-Pro-Gly-Ser-OH) on arousal in head injured mice, an animal model of unconsciousness. TRH, DN-1417, MK-771 and TSII-37 were injected 10 min before the head injury. TRH, DN-1417 and MK-771 caused dose-dependent decreases in the time required for recovery of the righting reflex time and in the time from the head injury to the onset of spontaneous movement. TSII-37 had no effect, when compared with the control group. In terms of the minimum effective dose, TRH and DN-1417 were of similar potency, but MK-771 was about 30-fold stronger than TRH. Measurement of the cross-reactivities of these TRH analogues by radiolabeled receptor assay suggest that the structure-binding relationship is proportional to the structure-activity relationship.
Tanaka
K
K
Department of Neurochemistry, Okayama University Medical School, Japan.
Ogawa
N
N
Chou
H
H
Mori
A
A
Yanaihara
N
N
D000818:Animals; D006259:Craniocerebral Trauma / Q000150:complications*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D014474:Unconsciousness / Q000188:drug therapy* / Q000209:etiology
D013973:Thyrotropin-Releasing Hormone