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, 178, 48-56

Imidazoline I 2 Receptors: An Update


Imidazoline I 2 Receptors: An Update

Jun-Xu Li. Pharmacol Ther.


Since first introduced more than two decades ago, the research in imidazoline I2 receptors has been steadily increasing. This review provides an update on the current status of I2 receptor pharmacology. Imidazoline I2 receptors or I2 binding 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 I2 receptors have been primarily unveiled by the studies of selective I2 receptor ligands. Accumulating evidence suggests that I2 receptor ligands are effective analgesics for persistent and chronic painful conditions such as inflammatory, neuropathic and postoperative pain. One selective I2 receptor 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. I2 receptor ligands also demonstrate robust discriminative stimulus activity and induce a characteristic discriminative cue in animals. Biochemical and preclinical in vivo investigations also suggest that I2 receptor ligands have neuroprotective activity and modulate body temperature. The emerging discrepancies of a range of purported selective I2 receptor ligands suggest different pharmacological effects mediated by discrete I2 receptor components which likely attribute to the I2 receptor-related proteins. It is proposed that the I2 receptors 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.

Keywords: Body temperature; Drug discrimination; Imidazoline I(2) receptor; Neuroprotection; Pain.

Conflict of interest statement

Conflict of Interest

The author declares no conflict of interest.


Figure 1
Figure 1
Left: cumulative publications in PubMed using search term “imidazoline receptors OR imidazoline binding sites”; right: cumulative publications in PubMed using search terms “imidazoline I1 receptors OR imidazoline I1 binding sites OR I1-imidazoline” and “imidazoline I2 receptors OR imidazoline I2 binding sites OR I2-imidazoline”, respectively.

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