Chronic oral administration of CG-3703, a thyrotropin releasing hormone analog, increases wake and decreases cataplexy in canine narcolepsy

The effects on cataplexy and daytime sleep of acute and chronic oral admini stration of CG-3703, a potent TRH analog were assessed in canine narcolepsy . CG-3703 was found to be orally active and to reduce cataplexy (0.25 to 16 mg/kg) and sleep (8 and 16 mg/kg) in a dose-dependent manner. Two-week ora l administration of CG-3703 (16 mg/kg) significantly reduced cataplexy and daytime sleep. The anticataplectic effects of CG-3703 were not associated w ith changes in general behavior, heart rate, blood pressure, rectal tempera ture, blood chemistry and thyroid function. Although drug tolerance for the effects on cataplexy and sleep were observed during the second week of chr onic drug administration, therapeutic efficacy on cataplexy was improved wi th individual dose adjustment (final dose range: 16 to 28 mg/kg, p.o.). The se results suggest that TRH analogs could be a promising new form of treatm ent for human narcolepsy. [Neuropsychopharmacology 23:34-45, 2000] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.