Over the past few years, a vast amount of research has shed light on the pharmacology of imidazoline binding sites (I-BS). To date, at least three classes of imidazoline binding sites have been characterised in accordance to their localisation, drug selectivity, proposed signalling pathways and functional roles. The existence of these sites raises the question as to whether an endogenous modulator exists. The identification of an endogenous extract denoted as clonidine displacing substance prompted the search for the active ingredient capable of mimicking the action of selective ligands at these sites. A number of candidates have been isolated and their functional activities have been assessed at these sites. Such endogenous ligands include agmatine, imidazoleacetic acid ribotide and the β-carboline harmane. As of yet, no consensus has been made to confirm the identity of the endogenous ligand at I-BS. The current review collates and reports what is known about these substances and their functional significance at I-BS.
Haya Abu Ghazaleh, Robin J. Tyacke and Alan L. Hudson