Metabolically stable receptor antagonists that are subtype selective are indispensable pharmacological tools. In this article, Philip Portoghese describes the bivalent ligand approach to drug design which has resulted in the development of several highly selective non-peptide opioid receptor antagonists, such as the κ-selective norbinaltorphimine and the δ-selective naltrindole. Models used resemble Schwyzer's message-address concept which originally described the recognition elements of peptide hormones; their success augurs well for the possibility of altering antagonist selectivity in a predictable fashion by simulating a portion of the address peptide component with a rigid non-peptide moiety.
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This work was supported by the National Institute on Drug Abuse.
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