Imidazoline I2receptors: An update.
Since first introduced more than two decades ago, the research in imidazoline I2receptors has been steadily increasing. This review provides an update on the current status of I2receptor pharmacology. Imidazoline I2receptors or I2binding sites refer to several (at least four) different proteins that bind to [3H]-idazoxan and [3H]-2-BFI with high affinity. The molecular identities of the proteins remain elusive. One of the proteins (45kD) seems to be consistent with the identity of brain creatine kinase. The biological functions of I2receptors have been primarily unveiled by the studies of selective I2receptor ligands. Accumulating evidence suggests that I2receptor ligands are effective analgesics for persistent and chronic painful conditions such as inflammatory, neuropathic and postoperative pain. One selective I2receptor ligand, CR4056, has been advanced to phase II clinical trial with the therapeutic indication of chronic inflammatory pain (osteoarthritis). The expansion to the treatment of other chronic pain conditions should be expected if CR4056 could eventually be approved as a new drug. I2receptor ligands also demonstrate robust discriminative stimulus activity and induce a characteristic discriminative cue in animals. Biochemical and preclinical in vivo investigations also suggest that I2receptor ligands have neuroprotective activity and modulate body temperature. The emerging discrepancies of a range of purported selective I2receptor ligands suggest different pharmacological effects mediated by discrete I2receptor components which likely attribute to the I2receptor-related proteins. It is proposed that the I2receptors represent an emerging drug target for the treatment of neurological disorders such as pain and stroke, and deserve more research attention to translate preclinical findings to pharmacotherapies.
School of Pharmacy, Nantong University, Nantong, Jiangsu Province, China; Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA. Electronic address: junxuli@buffalo.edu.
Jun-Xu
JX
Li
D000818:Animals; D006801:Humans; D054755:Imidazoline Receptors / Q000378:metabolism*; D008024:Ligands
D054755:Imidazoline Receptors; D008024:Ligands
Body temperature; Drug discrimination; Imidazoline I(2) receptor; Neuroprotection; Pain