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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Imidazoline receptors, novel agents and therapeutic potential.

The initial realization that agents containing an imidazoline structure may interact with a distinct class of receptors, has led to a major class of cardiovascular agents, which now has the potential to enter a third generation. There is now general acceptance that there are three main imidazoline receptor classes, the I(1) imidazoline receptor which mediates the sympatho-inhibitory actions to lower blood pressure, the I(2) receptor which is an important allosteric binding site of monoamine oxidase and the I(3) receptor which regulates insulin secretion from pancreatic beta cells. Thus all three represent important targets for cardiovascular research. Interestingly, an I(1)- receptor candidate has been cloned (IRAS, imidazoline receptor antisera selected) which is a homologue of the mouse cell adhesion integrin binding protein Nischarin. There has been range of new agonists and antagonists with very high selectivity for I(1), I(2) and I(3) receptors developed. Three different endogenous ligands have been characterized including agmatine (decarboxylated arginine), a range of beta-carbolines including harman and harmane, and more recently imidazoleacetic acid-ribotide. The imidazoline field has recently seen an enormous diversification with discoveries that I(1) and I(2) receptors also play a role in cell proliferation, regulation of body fat, neuroprotection, inflammation and some psychiatric disorders such as depression. This diversification has continued with the addition of effective agents with imidazoline affinity in the fields of cancer, pain and opioid addiction, stress, cell adhesion, epilepsy and appetite. The imidazoline field has maturated considerably with a range of highly selective leader molecules, candidate receptors and endogenous ligands. We are therefore only at the threshold of an exciting new era as we begin to understand the diverse and complex nature of their function.[1]


  1. Imidazoline receptors, novel agents and therapeutic potential. Head, G.A., Mayorov, D.N. Cardiovascular & hematological agents in medicinal chemistry. (2006) [Pubmed]
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