Binding a critical pentapeptide region on the scaffolding protein filamin A regulates signaling of mu opioid receptors (MORs) so that their activation should not result in the opioid tolerance, dependence and addiction associated with current opioid painkillers. Additionally, we show that compounds that bind this site on filamin A reduce release of inflammatory cytokines. PTI-609 is a new chemi...

The endogenous opioids met- and leu-enkephalin are inactivated by peptidases preventing the activation of opioid receptors. Inhibition of enkephalin-degrading enzymes increases endogenous enkephalin levels and stimulates robust behavioral effects. RB101, an inhibitor of enkephalin-degrading enzymes, produces antinociceptive, antidepressant, and anxiolytic effects in rodents, without typical opi...

background and objectives cannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. there are also functional interactions between both cannabinoid and opioid systems. in this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system.   methods in the present study, we investigated the ...

Methods The chemistry involved the design and synthesis of two sets of oxazolomorphinans having the new heteroring anellated to the A-ring of the morphinan backbone. Binding affinities of the newly synthesized compounds at opioid receptors were determined by in vitro competition binding assays using rat brain (μ, δ) and guinea pig brain ( ) membranes and employing [H]DAMGO (μ), [H] [Ile]deltorp...

The discovery of the endogenous opioid peptide systems and their subsequent identification in human cerebrospinal fluid near 30 years ago triggered an intensive research to evaluate the function of these compounds in the clinical perspective. However, for this purpose it was necessary to develop reliable techniques with high sensitivity and reproducibility. Furthermore, it was necessary to asse...

The discovery of numerous endogenous neuropeptides that participate in the formation, transmission, modulation, and perception of pain signals offers numerous strategies for the development of new analgesics. Nevertheless, the same research has not yet replaced opioids as the gold standard of pain treatment. Therefore, one possible avenue of drug development may shift interest from searching fo...

Regulation of the mu-opioid receptor gene by opioid analgesic drugs has not been observed in rats and mice following in vivo treatments that produce tolerance. Although in vivo heterologous regulation of mu-opioid receptor mRNA by non-opioid compounds has been reported, the failure to observe changes in mu-opioid receptor mRNA levels in vivo after treatment with opioid agonists raised the possi...

Opiates are indispensable for the treatment of moderate to severe pain. The gastrointestinal tract is one of the major victims of the undesired effects of opiates, because the enteric nervous system expresses all major subtypes of opioid receptors. As a result, propulsive motility and secretory processes in the gut are inhibited by opioid analgesics, and the ensuing constipation is one of the m...

Background: Nor-BNI, GNTI and JDTic induce selective k opioid antagonism that is delayed and extremely prolonged, but some other effects are of rapid onset and brief duration. The transient effects of these compounds differ, suggesting that some of them may be mediated by other targets. Results: In binding assays, the three antagonists showed no detectable affinity (Ki$10 mM) for most non-opioi...

A series of N,N'-disubstituted-2-nitroethene-1,1-diamine and N,N'-disubstituted- N''-cyanoguanidine derivatives were prepared and evaluated for in vivo analgesic activity. The blood brain barrier (BBB) VolSurf model was used to predict the BBB permeation profiles of our synthesized compounds. Some compounds show both remarkable analgesic activity and good BBB permeation profiles, and these comp...