Imidazoline receptor I2 (I2 receptor)

Imidazoline receptor I2 is a pharmacologically defined, heterogeneous group of mitochondrial and possibly cytosolic proteins, operationally characterized by high-affinity binding of radiolabeled idazoxan and 2-BFI, and by their lack of interaction with adrenergic receptors. Although frequently referred to as a receptor, the I2 "receptor" encompasses at least four distinct proteins—including monoamine oxidase isoforms and brain creatine kinase. Selective ligands for I2 receptors have demonstrated robust analgesic efficacy in animal models of persistent and chronic pain, and the lead candidate drug CR4056 is under clinical investigation for osteoarthritis pain. I2 receptor ligands show additional effects including hypothermia, cognitive modulation, and neuroprotection, likely through allosteric modulation of mitochondrial enzymes and partial inhibition of glutamatergic NMDA receptor activity. While I2 receptors are considered an emerging therapeutic target, the lack of a single confirmed protein identity and the functional heterogeneity among the constituent proteins complicate drug development and interpretation of pharmacological data.

Other names

I2 binding siteImidazoline I2 receptorI2 site

Agonism or antagonism at I2 receptor binding sites; Allosteric modulation of monoamine oxidase activity (for a subset of I2 sites); Modulation of NMDA receptor activity