Pharmacology of Itch

Alan Cowan, George B. Kehner, Saadet Inan, Cowan, Alan, Kehner, George B., Inan, Saadet

Several chemically diverse pruritogens, including bombesin, compound 48/80, norbinaltorphimine, and 5'-GNTI, cause rodents to scratch excessively in a stable, uniform manner and consequently provide convenient animal models of itch against which potential antipruritics may be evaluated, structure-activity relationships established, and the nature of spontaneous, repetitive behavior itself analyzed. Decreasing the number of scratching bouts in these apparently simple models has been the requisite first step in the progress of kappa opioid agonists such as nalbuphine, asimadoline, and CR845 toward clinical testing as antipruritics. Nalfurafine is the prime example of a kappa agonist spanning the developmental divide between scratching mice models and commercialization within 10 years. Patients undergoing hemodialysis and suffering from the itching associated with uremic pruritus, and potentially those inflicted with atopic dermatitis, are the beneficiaries.