[Montirelin hydrate (NS-3), a TRH analog, improved the disturbance of consciousness caused by head concussion and pentobarbital in mice].
Effects of a novel TRH analog, montirelin hydrate (NS-3), on the coma caused by head concussion and narcosis induced by pentobarbital were compared with those of TRH in mice. Head concussion caused a behavioral comatose state with loss of the righting reflex and spontaneous motor activity. NS-3 shortened the latent periods to the recovery of the righting reflex (0.03-0.1 mg/kg, i.v.) and spontaneous motor activity (0.1 mg/kg, i.v.) following the head concussion. In the case of TRH, higher doses were needed to induce such effects. NS-3 (0.1-0.3 mg/kg, i.v.) reversed the pentobarbital-induced narcosis in a dose-dependent manner. A similar effect was elicited by 30- to 100-fold higher doses of TRH than NS-3. The analeptic effect of NS-3 in the pentobarbital-narcotized mice was antagonized by SCH23390, a dopamine D1 antagonist or by the combined treatment with prazosin and scopolamine, while neither prazosin nor scopolamine alone antagonized the analeptic effect of NS-3. Taken together with the finding that NS-3 did not bind to dopamine, adrenaline or muscarine receptors, it is suggested that NS-3 may restore the disturbance of consciousness by activating the brain dopamine, noradrenaline and acetylcholine neurons without stimulating these receptors directly.
Mushiroi
T
T
Research Laboratories, Nippon Shinyaku Co. Ltd., Kyoto, Japan.
Shibahara
R
R
Tamura
M
M
Shimizu
T
T
Itoh
Y
Y
Ukai
Y
Y
Yoshikuni
Y
Y
Kimura
K
K
D000758:Anesthesia; D000818:Animals; D001924:Brain Concussion / Q000150:complications*; D003244:Consciousness Disorders / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010424:Pentobarbital / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D017983:Receptors, Catecholamine / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D017983:Receptors, Catecholamine; D018079:Receptors, GABA; D011976:Receptors, Muscarinic; D011957:Receptors, Opioid; C031926:montirelin; D013973:Thyrotropin-Releasing Hormone; D010424:Pentobarbital