Delta-selective ligands related to naltrindole

Opioid antagonists have been crucial as pharmacological tools in opioid research [1]. Historically, the ability of naloxone or naltrexone to reversibly antagonize an opioid agonist effect in an apparently competitive fashion was an important criterion for establishing the involvement of an opioid receptormediated effect. Naloxone and naltrexone are useful in this regard because they are universal antagonists; that is, they are able to antagonize the agonist effects mediated through multiple opioid receptors. However, because these ligands possess low selectivity, they are not useful for investigating the pharmacology mediated through specific opioid receptor types. Consequently, an armamentarium of highly selective opioid antagonists is now available for this purpose. Such antagonists have been invaluable for determining the selectivity of opioid ligands and opioid receptor mechanisms. In this chapter we focus on the rationale for the design of nonpeptide, deltaselective opioid antagonists related to naltrindole and their utility as pharmacological tools.