Imidazoline receptors are the primaryreceptors on whichclonidine and otherimidazolines act.[1][2][3] There are three main classes of imidazoline receptor: I1 is involved in inhibition of thesympathetic nervous system to lower blood pressure,[4] I2 has as yet uncertain functions but is implicated in several psychiatric conditions,[5][6] and I3 regulates insulin secretion.[7]
Animal research suggests that much of the antihypertensive action ofimidazoline drugs such asclonidine is mediated by the I1 receptor.[8][10][11] In addition, I1 receptor activation is used inophthalmology to reduce intraocular pressure.[8] Other putative functions include promoting Na+ excretion and promoting neural activity duringhypoxia.[8]
The I2 receptor binding sites have been defined as being selective binding sites inhibited by the antagonistidazoxan that are not blocked bycatecholamines.[12] The major binding site is located on the outer mitochondrial membrane, and is proposed to be anallosteric site onmonoamine oxidase, while another binding site has been found to be braincreatine kinase.[12][8] Other known binding sites have yet to be characterized as of 2017[update].[12][13]
Preliminary research in rodents suggests that I2 receptor agonists may be effective in chronic, but not acute pain, includingfibromyalgia.[12] I2 receptor activation has also been shown todecrease body temperature, potentially mediating neuroprotective effects seen in rats.[12]
The only known antagonist for the receptor isidazoxan, which is non-selective.[12][8]
^Regunathan, S; Reis, D J (April 1996). "Imidazoline Receptors and Their Endogenous Ligands".Annual Review of Pharmacology and Toxicology.36 (1):511–544.doi:10.1146/annurev.pa.36.040196.002455.PMID8725400.
^Kawamura, Kazunori; Shimoda, Yoko; Kumata, Katsushi; Fujinaga, Masayuki; Yui, Joji; Yamasaki, Tomoteru; Xie, Lin; Hatori, Akiko; Wakizaka, Hidekatsu; Kurihara, Yusuke; Ogawa, Masanao; Nengaki, Nobuki; Zhang, Ming-Rong (April 2015). "In vivo evaluation of a new 18F-labeled PET ligand, [18F]FEBU, for the imaging of I2-imidazoline receptors".Nuclear Medicine and Biology.42 (4):406–412.doi:10.1016/j.nucmedbio.2014.12.014.PMID25583220.
^Head, G.; Mayorov, D. (1 January 2006). "Imidazoline Receptors, Novel Agents and Therapeutic Potential".Cardiovascular & Hematological Agents in Medicinal Chemistry.4 (1):17–32.doi:10.2174/187152506775268758.PMID16529547.
^abcdefghijklmErnsberger, P; Graves, ME; Graff, LM; Zakieh, N; Nguyen, P; Collins, LA; Westbrooks, KL; Johnson, GG (12 July 1995). "I1-imidazoline receptors. Definition, characterization, distribution, and transmembrane signaling".Annals of the New York Academy of Sciences.763:22–42.doi:10.1111/j.1749-6632.1995.tb32388.x.PMID7677333.S2CID85739305.
^McDonald, GR; Olivieri, A; Ramsay, RR; Holt, A (December 2010). "On the formation and nature of the imidazoline I2 binding site on human monoamine oxidase-B".Pharmacological Research.62 (6):475–88.doi:10.1016/j.phrs.2010.09.001.PMID20832472.
^Morgan, NG; Chan, SL (September 2001). "Imidazoline binding sites in the endocrine pancreas: can they fulfil their potential as targets for the development of new insulin secretagogues?".Current Pharmaceutical Design.7 (14):1413–31.doi:10.2174/1381612013397366.PMID11472276.
