Histamine exerts a range of effects on many physiological and pathological processes and new roles are still being elucidated. The best characterized roles of histamine are those in (allergic) inflammation, gastric acid secretion and as a neurotransmitter. The four histamine receptors known to date (H1-H4) all belong to the large family of G-protein coupled receptors (GPCR-A18).
Activation of the H1 receptor results in elevated levels of inositol phosphate through coupling to the Gq protein. These receptors are expressed on multiple cell types including endothelial cells and smooth muscle cells, where they mediate vasodilatation and bronchoconstriction. Antagonists of H1 receptors have been used for many years in the treatment of allergic inflammatory responses.
H2 receptors activate Gs (actually member of GPCR-A17 family) and increase cyclic AMP formation. They regulate various functions of histamine, including heart contraction, gastric acid secretion, cell proliferation and differentiation, and immune responses.
H3 receptors mediate their function through Gi/o proteins, leading to inhibition of cAMP formation, enhancing calcium mobilization and activating mitogen-activated protein kinases (MAPKs) and ion channels. Their activation stimulates the negative feedback mechanism that reduces central histaminergic activity. Besides, this subtype seems to play roles in cognition, sleep-wake status, obesity and (neuro-) inflammation.
Activation of the H4 receptor in primary cells appears to be mainly coupled to pertussis-toxin-sensitive Gi/o proteins, which signal through increases in intracellular calcium. Although there is still much work to be done to uncover the function of the H4 receptor, it has been implicated in mast cell, eosinophil and dendritic cell chemotaxis, as well as cytokine production from T cells and dendritic cells. The development of ligands selectively interacting at this receptor, such as JNJ 7777120 (Axon 1306), and JNJ 10191584 (Axon 1307) can play an important role in revealing the biological function of the most recent member of the family of histamine receptors.
 The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. R.L. Thurmond, E.W. Gelfand, P.J. Dunford. Nature Rev. Drug Discov. 2008, 7, 41-53.
 Definition and antagonism of histamine H2-receptors. Black, J. W., Duncan, W. A. M., Durant, C. J., Ganellin, C. R. & Parsons, E. M. Nature 1972, 236, 385–390.
 The histamine H3 receptor: from gene cloning to H3 receptor drugs. Leurs, R., Bakker, R. A., Timmerman, H.,de Esch, I. J. P. Nature Rev. Drug Discov. 2005, 4, 107–120.
 Development and chemistry of histamine H4 receptor ligands as potential modulators of inflammatory and allergic responses. Venable, J. D., Thurmond, R. L. Antiinflamm. Antiallergy Agents Med. Chem. 2006, 5, 307–322.
|Axon ID||Name||Description||From price|
|1503||Asenapine maleate||Atypical antipsychotic||€75.00|
|2458||Clemizole||Inhibitor of the transient receptor potential channel TRPC5||€75.00|
|1445||Dimebon||Alzheimer's disease therapeutic||€65.00|
|1453||Fexofenadine hydrochloride||H1 antagonist||€55.00|
|2486||JZP 361||Selective reversible inhibitor of MAGL with Histamine H1 antagonistic activity||€125.00|
|1354||Quetiapine fumarate||Atypical antipsychotic||€75.00|