Nonpeptidic delta opioid antagonists

TABLE 2 Nonpeptide Delta Opioid Antagonists/Inverse Agonists... 

The structures of selected peptide and nonpeptide delta-selective opioid antagonists are shown in Figure 1. However, although the compounds shown in Figure 1 have been introduced as neutral delta opioid antagonists, data from more sensitive functional assay systems have subsequently proven that these compounds are also capable of behaving as inverse agonists at the delta opioid receptor under appropriate conditions. 

Fig. 1 Structures of the delta opioid antagonist Naltrindole and of prototypic nonpeptidic delta opioid agonists...

Several nonpeptide delta opioid receptor antagonists are currently under investigation in this project, including 7-benzylidene-7-dehydronaltrexone HCl (BNTX), naltrindole (NTI), and naltriben (NTB). In vitro exposure to BNTX or NTI results in immunosuppression at concentrations between 0.1 and 10 M, consonant with the hypothesis that delta opioid receptor agonists enhance, but delta receptor antagonists suppress, immune functional parameters. In comparison, in vitro exposure to NTB did not result in any detectable alteration in immune function. 

Figure 3 An approach to the design of a nonpeptide, delta-selective opioid antagonist based on the message-address concept. The message and address components of the delta-selective peptide enkephalin (upper) are compared to those in an opiate (lower).

Nonpeptidic Delta (8) Opioid Agonists and Antagonists of the Diarylmethylpiperazine Class What Have We Learned . 121... 

Takemori et al. (1992) introduced two highly selective nonpeptide delta (OPj) opioid antagonists for the delta receptors exclusively, as illustrated below i.e., naltrindol, and naltiben. 

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