The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Additional isoforms seem to exist. Expressed abundantly in brain, most notably throughout the thalamus, the ventromedial hypothalamus and the caudate nucleus. Isoform 1 is largely predominant in all tissues. Proxyfan acts as a potent neutral antagonist while thioperamide, ciproxifan and FUB465 act as potent inverse agonists. Belongs to the G-protein coupled receptor 1 family.