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). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization. Additional isoforms seem to exist. Expressed predominantly in the CNS, with the greatest expression in the thalamus and caudate nucleus. The various isoforms are mainly coexpressed in brain, but their relative expression level varies in a region-specific manner. Isoform 3 and isoform 7 are highly expressed in the thalamus, caudate nucleus and cerebellum while isoform 5 and isoform 6 show a poor expression. Isoform 5 and isoform 6 show a high expression in the amygdala, substantia nigra, cerebral cortex and hypothalamus. Isoform 7 is not found in hypothalamus or substantia nigra. Does not bind to cimetidine and tripolidine. Shows modest affinity for thioperamide, imetit, N-alpha-methylhistamine and R(-)-alpha-methylhistamine. Isoform 4 is unable to bind to iodoproxyfan while isoforms 1 and 3 bind it with high affinity. Belongs to the G-protein coupled receptor 1 family.