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.