H3 Histamine Receptor couples to Gi/G0 proteins and receptor activation leads to inhibition of adenylate cyclase, activation of the mitogen-activated protein kinase (MAPK) cascade and inhibition of the Na+/H+ exchanger. nH3 receptors are expressed primarily in the central nervous system (CNS) where they are located in presynaptic membranes of histaminergic neurons, where they negatively regulate the synthesis and release of histamine. In addition, H3 receptors are also located on nonhistaminergic neurons, where they regulate the release of other amines such as dopamine, serotonin, and norepinephrine. nBased on these studies, a central role for H3 receptors has been proposed in disorders involving cognition such as attention deficit and hyperactivity disorder (ADHD), Alzheimer disease and schizophrenia as well as sleep and energy homeostasis (i.e. obesity) disorders
