Seeing through a glass darkly': casting light on imidazoline `I' sites

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 19; no. 9; pp. 381 - 390
• Main Authors: Eglen, Richard M., Hudson, Alan L., Kendall, David A., Nutt, David J., Morgan, Noel G., Wilson, Vince G., Dillon, Michael P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.1998
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - pharmacology; agmatine; Agmatine - chemistry; Allosteric Site - drug effects; Animals; Binding, Competitive; Brain - drug effects; Brain - enzymology; Clonidine - chemistry; clouidine displacing substance; Down-Regulation; Imidazoles - chemistry; Imidazoles - metabolism; Imidazoles - pharmacology; imidazoline sites; Kidney - drug effects; Kidney - metabolism; monoamine oxidase; Monoamine Oxidase - chemistry; Monoamine Oxidase - metabolism; Neuroprotective Agents - pharmacology; Structure-Activity Relationship; clouidine displacing substance; imidazoline sites; monoamine oxidase; agmatine
• DOI: 10.1016/S0165-6147(98)01244-9
• ISSN: 0165-6147

Although imidazoline sites have been the subject of research for several years, there is still controversy about their structure, diversity and physiology. The I 1 site is thought to exist principally as a binding site and is widely purported to play a role in controlling systemic blood pressure, although this is still unclear. The majority of I 2 sites are widely accepted as being allosteric sites on monoamine oxidase; however, even with selective ligands, their exact function remains to be determined. A putative I 3 site modulates insulin secretion and could represent the first functional site to be pharmacologically defined with selective agonists and antagonists. The structure and relevance of the proposed endogenous ligand `clonidine-displacing substance' remains elusive. A potential candidate for this substance is agmatine; however, although it is capable of displacing bound clonidine from imidazoline sites, it lacks the functionality ascribed to the clonidine-displacing substance. In this review, Richard M. Eglen and colleagues assess our knowledge of imidazoline sites in the light of recent data.