ICI-204,448 hydrochloride (CAS 121264-04-8)

ICI-204,448 hydrochloride (CAS 121264-04-8) is a chemical compound primarily recognized for its role as a kappa-opioid receptor (KOR) agonist. A notable aspect of ICI-204,448 is its action at peripheral kappa-opioid receptors, as opposed to central nervous system receptors. This peripheral activity is because it suggests that the compound can exert its effects without inducing the central side effects, such as sedation or dysphoria, often associated with central opioid receptor activation. This feature was highlighted in one of the studies (PMID: 15687734), where ICI-204,448 was shown to induce hypothermia in rats at cold temperatures, underscoring its influence on thermoregulation through peripheral kappa-opioid receptors. Another study (PMID: 24113749) aimed to identify new kappa-opioid receptor (KOR) agonists that are functionally selective, meaning they can activate specific signaling pathways without triggering adverse effects. The researchers used a combination of in silico and parallel screening approaches to identify several novel KOR-selective ligand scaffolds. These findings could lead to the development of more effective analgesics that avoid the adverse effects associated with some KOR agonists.