Histamine has been implicated in a variety of biological functions including thermo- and immunoregulation, food intake, hyperexcitability, pain transmission, arousal, reward, memory, and emotional responses. The histamine H3 receptor is a Gi-coupled presynaptic auto- and hetero-receptor whose activation leads to a decreased release of histamine, glutamate, norepinephrine, and acetylcholine in the brain. H3R antagonists are expected to increase the release of these neurotransmitters, which may contribute therapeutic benefit in diseases characterized by sleep/wake disturbances or cognitive disorders. JNJ-5207852 is a selective, non-imidazole histamine H3R antagonist with high affinity at the rat (pKi = 8.9) and human (pKi = 9.24) H3 receptors. In rodents, 1-10 mg/kg JNJ-5207852 administered subcutaneously increases time spent awake and decreases REM sleep and slow-wave sleep.
