Delta receptors morphine

The relative extent of the unwanted effects caused by selective agonists at the different opioid receptors is of great importance in determining if non-mu opioids will have better spectra of actions as compared to morphine. However, there are good indications that the kappa and delta receptor agonists cause less respiratory depression than mu... 

Sold as Dilaudid in the U.S., hydromorphone is a semisynthetic, differing from morphine only by presence of a 6-keto group, and the hydrogenation of the double bond at the 7-8 position of the molecule.57 Like morphine, it acts primarily at the mu opioid receptors, and to a lesser degree at delta receptors. 

The important role of delta receptors in the development of morphine tolerance and physical dependence has prompted the search for mixed mu... 

When the efficacy of biphalin-stimulated G protein activation was examined (Table 3) in delta opioid receptor-transfected CHO cells, an efficacy ratio of 0.42 was determined as compared with deltorphin-II and DPDPE, the latter a reference delta-selective agonist. Such low efficacy values suggest that biphalin does not efficiently stimulate the G protein through the delta receptor [9]. Relative affinities of biphalin and morphine for mu, delta, and kappa binding sites in guinea pig brain membranes are shown in Table 4. 

Interestingly, morphine is primarily considered to have selective effects on the mu opioid receptor for its analgesic effects however, there is also evidence that it possesses effects on delta or kappa opioid receptors and that crosstalk can occur between mu and delta opioid receptors [44]. To test the hypothesis that the cardioprotective effects of IPC and morphine were acting via a delta opioid receptor, Schultz et al. [45] administered the selective delta receptor antagonist naltrindole to rats prior to IPC or morphine infusion. In both instances, the cardioprotective effects of morphine and IPC were completely abolished at a dose of naltrindole that had no effect by itself on infarct size in nonpreconditioned rat hearts. These data clearly suggest that both IPC and morphine are exerting their cardioprotective effects via the delta opioid receptor in the intact rat heart. 

Studies in animals and primates with these highly selective delta agonists begin to reveal that unlike mu opioid agonists such as morphine, oxy-contin, fentanyl, etc., agents acting at the delta receptor are unlikely to produce addictive liability and respiratory depression. In fact, delta agonists may actually counteract those side effects induced by mu opioids. 

Riba P, Ben Y, Smith AP, Furst S, Lee NM (2002) Morphine tolerance in spinal cord is due to interaction between mu- and delta-receptors. J Pharmacol Exp Ther 300 265-272 Smith FL, Javed RR, Elzey MJ, Dewey WL (2003) The expression of a high level of morphine antinociceptive tolerance in mice involves both PKC and PKA. Brain Res 985 78-88... 

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