Inverse agonism at the delta opioid receptors

According to the traditional concept of agonist activity, agonist occupation of the receptor is a fundamental condition of receptor activation [1]. The ternary complex model furthermore postulates that in order to produce a cellular response, the agonist-receptor complex should interact with a third, guanine nucleotide-sensitive binding partner (guanine nucleotide binding, or G protein) [2]. According to this classical concept, two classes of physiologically active ligands can be anticipated: agonists, and competitive antagonists. Synthetic agonists are thought to interact with the receptors the same way as endogenous hormones, and produce identical physiological response (the '‘pharmacophore’' concept, reviewed in [3]. Competitive antagonists share the receptor binding site with agonists, but are not able to promote the formation of the ternary complex. Therefore, competitive antagonists pro-duce physiological response by competing with the endogenous agonist for the common receptor binding site.