@article {Monczormol.116.105981, author = {Federico Monczor and Natalia Fernandez}, title = {Current Knowledge and Perspectives for Histamine H1 and H2 Receptor Pharmacology. Functional Selectivity, Receptor Crosstalk and Repositioning of Classic Histaminergic Ligands.}, elocation-id = {mol.116.105981}, year = {2016}, doi = {10.1124/mol.116.105981}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {H1 and H2 histamine receptor antagonists, although developed many decades ago, are still effective for the treatment of allergic and gastric acid-related conditions. The aim of the present article is to focus on novel aspects of the pharmacology and molecular mechanisms of histamine receptors that should be contemplated for either optimizing current therapies, repositioning histaminergic ligands for new therapeutic uses or even for including agonists of the histaminergic system in the treatment of different pathologies as leukemia or neurodegenerative disorders. In the last years there have been described new signaling phenomena related to H1R and H2R that make them suitable for novel therapeutic approaches. Crosstalk between histamine receptors and other membrane or nuclear receptors can be envisaged as a way to modulate other signaling pathways and to potentiate the efficacy of drugs acting on different receptors. Likewise, biased signaling at histamine receptors appears as a pharmacological feature that can be exploited to look into non-traditional therapeutic uses for H1 and H2 biased agonists in malignancies such as Acute Myeloid Leukemia and to avoid undesired side effects when used in standard treatments. We hope that the molecular mechanisms discussed in the present review contribute to a better understanding of the different aspects involved in histamine receptor pharmacology, which in turn shall contribute to increase drug efficacy, avoid adverse effects or reposition histaminergic ligands.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/early/2016/09/13/mol.116.105981}, eprint = {https://molpharm.aspetjournals.org/content/early/2016/09/13/mol.116.105981.full.pdf}, journal = {Molecular Pharmacology} }