Effects of IV and ICV Hypocretin-1 (Orexin A) in Hypocretin Receptor-2 Gene Mutated Narcoleptic Dogs and IV Hypocretin-1 Replacement Therapy in a Hypocretin-ligand-deficient Narcoleptic Dog

Abstract

Hypocretin-1 administration, by central and systemic routes, does not improve narcoleptic symptoms in Hcrtr2 mutated Dobermans. Systemic hypocretin-1 hardly crosses the blood-brain barrier to produce therapeutic effects. The development of more centrally penetrable and longer lasting hypocretin analogs will be needed to further explore this therapeutic pathway in humans.