Histamine is an inflammatory mediator that is ubiquitously expressed and has a broad range of pharmacologic effects. Specifically, it plays a role in the central nervous, gastrointestinal, respiratory and immune systems. The effects of histamine are mediated by a family of G protein-coupled receptors,the Histamine H1, H2, H3 and H4 Receptors. The gene encoding the human Histamine H3 Receptor is located on chromosome 20 and is expressed as six alternative splice variants in thalamus. These isoforms contain either a deletion in the second transmembrane domain or a variable deletion in the third intracellular loop. The existence of multiple H3 Receptor isoforms suggests that H3-mediated effects may be regulated through alternative splicing mechanisms.The H3 Receptor acts as an autoreceptor in the central nervous system (CNS) and modulates histamine synthesis and release.