In the study of pain research, they test for in vivo narcotic activity first using the "hot plate rat tail reflex" test. Before that a host of receptor binding tests are performed to determine, mu , kappa, delta and sigma opiod profile. I'm not totally up to date on all of this, but do know that kappa receptor binding is an indicator of how the compound will affect smooth muscle, and thus the "constipating effect" of a particular opiod. Constipation is an ugly side effect of opiods that hospitals would dearly like to eliminate, and would be a godsend to chronic pain patients (and , yes, those who like to take opiods recreationally).
Since research in CNS active compounds these days is usually to find a more "Selective" compound, why hasn't anyone come up with an opiod that has a high mu binding profile, with little kappa binding and an acceptable delta and sigma profile? It would seem that this could be done, especially in the "non-phenanthrene" classes of opiates.
Since research in CNS active compounds these days is usually to find a more "Selective" compound, why hasn't anyone come up with an opiod that has a high mu binding profile, with little kappa binding and an acceptable delta and sigma profile? It would seem that this could be done, especially in the "non-phenanthrene" classes of opiates.
, or a glycerin supository. 
spontaneous bowel movements (SBMs)/week (with 25% accompanied by a sensation of incomplete evacuation, straining, or lumpy hard stools), requiring analgesia equivalent to 30mg oral morphine/day were randomized to alvimopan 0.5mg twice daily (BID), 1mg once daily (QD), 1mg BID, or placebo for 6 weeks. Compared with placebo, there was a statistically and clinically significant increase in mean weekly SBM frequency over the initial 3 weeks of treatment (primary endpoint) with alvimopan 0.5mg BID (+1.71 mean SBMs/week), alvimopan 1mg QD (+1.64) and alvimopan 1mg BID (+2.52); P<0.001 for all comparisons. Increased SBM frequency and additional treatment effects, including improvements in symptoms such as straining, stool consistency, incomplete evacuation, abdominal bloating/discomfort, and decreased appetite, were sustained over 6 weeks. The most frequently reported adverse events were abdominal pain, nausea, and diarrhea, occurring more frequently in the higher dosage groups. The alvimopan 0.5mg BID regimen demonstrated the best benefit-to-risk profile for managing OBD with alvimopan in this study population, with a side effect profile similar to that of placebo. There was no evidence of opioid analgesia antagonism. Competitive peripheral antagonism of opioids with alvimopan can restore GI function and relieve OBD without compromising analgesia.