Imidazoline receptors are the primary
receptors on which
clonidine and other
imidazolines act.[1][2][3] There are three main classes of imidazoline receptor: I1 is involved in inhibition of the
sympathetic 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]
Classes
As of 2017, there are three known subtypes of imidazoline receptors: I1, I2, and I3.
Animal research suggests that much of the antihypertensive action of
imidazoline drugs such as
clonidine is mediated by the I1 receptor.[8][10][11] In addition, I1 receptor activation is used in
ophthalmology to reduce intraocular pressure.[8] Other putative functions include promoting Na+ excretion and promoting neural activity during
hypoxia.[8]
I2 receptor
The I2 receptor binding sites have been defined as being selective binding sites inhibited by the antagonist
idazoxan that are not blocked by
catecholamines.[12] The major binding site is located on the outer mitochondrial membrane, and is proposed to be an
allosteric site on
monoamine oxidase, while another binding site has been found to be brain
creatine 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, including
fibromyalgia.[12] I2 receptor activation has also been shown to
decrease body temperature, potentially mediating neuroprotective effects seen in rats.[12]
The only known antagonist for the receptor is
idazoxan, 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.
^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.