RT Journal Article
SR Electronic
T1 Effects of Thyrotropin-Releasing Hormone and Its Analogs on Daytime Sleepiness and Cataplexy in Canine Narcolepsy
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6401
OP 6408
DO 10.1523/JNEUROSCI.17-16-06401.1997
VO 17
IS 16
A1 Seiji Nishino
A1 Janis Arrigoni
A1 Jeff Shelton
A1 Takashi Kanbayashi
A1 William C. Dement
A1 Emmanuel Mignot
YR 1997
UL http://www.jneurosci.org/content/17/16/6401.abstract
AB The therapeutic potential of thyrotropin-releasing hormone (TRH) and TRH analogs in narcolepsy, a sleep disorder characterized by abnormal rapid eye movement (REM) sleep and daytime sleepiness, was examined using the canine model. The effects of TRH and the biologically stable TRH analogs CG3703, CG3509, and TA0910 on daytime sleep and cataplexy, a symptom of abnormal REM sleep, were assessed using polysomnographic recordings and the food elicited cataplexy test (FECT), respectively. CG3703 (100 and 400 μg/kg, i.v.) and TA0910 (100 and 400 μg/kg, i.v.) significantly increased wakefulness and decreased sleep in narcoleptic canines, whereas TRH (400 and 1600 μg/kg, i.v.) had no significant effect. TRH (25–1600 μg/kg, i.v.) and all three TRH analogs, CG3703 (6.25–400 μg/kg, i.v., and 0.25–16 mg/kg, p.o.), CG3509 (25–1600 μg/kg, i.v.), and TA0910 (25–1600 μg/kg, i.v.), significantly reduced cataplexy in canine narcolepsy. These compounds did not produce any significant side effects during behavioral assays, nor did they alter free T3 and T4 levels in serum even when used at doses that completely suppressed cataplexy. Although more work is needed to establish the mode of action of TRH analogs on alertness and REM sleep-related symptoms, our results suggest a possible therapeutic application for TRH analogs in human sleep disorders.