MobiusDick
Bluelighter
I'm not going to cite references today bc I got the COVID mRNA vaccine & 2nd Shingles Vax yesterday & my temp is ~ 104 F .
I've been thinking a lot about this as I have been sampling very strong fentanyl analogues like isocarfentanil, lofentanil, sufentanil, & betahydroxyalphamethylfentanyl, as well as the piperazine based benzimidazole based nitazenes like metonitazene, isonitazene, N-pyrrolidino metonitazene and etonitazene lately & while it seems that Etonitazene is one of the strongest, the piperazine group causes extremely high anticholinergic effects, or some other receptor that causes dry mouth as it seems this is the effect that is way off the chart in relation to any other opiods . But aside from that, there seems to be a disconnect between the effect these drugs have on MOR and the effect that they have on Beta-arrestin-2. I believe when this disconnect occurs, the cell internalizes the MOR to downregulate & unless you administer the MOR antagonist or partial agonist quickly, the internalized MORs are not as naloxone /buprenorphine labile or susceptible. My results are anecdotal and as many of you who are aware of my history from Alt.Drugs.Hard and so on, As the Beta-Arrestin-2 Ki levels show higher binding affinity as well as Ki MOR levels going into pM and fM range. Carfentanil induced potent and extensive cell surface receptor loss, whilst the marked desensitisation of G protein-coupled inwardly rectifying potassium channel currents in the continued presence of carfentanil in neurones was prevented by a GRK2/3 inhibitor much more quickly than the other fentanyl derivatives, but when given time, the same thing happens, so it may be that some of these drugs are weaker GRK2/3 inhibitors in their own right. So my criticism of this study involves perhaps an autooxidation or reduction
MobiusDick
Here is a reference for you to look at and as soon as I feel better I will explain why I feel this way and possible changes to the study to confirm or disprove my suspicions
I've been thinking a lot about this as I have been sampling very strong fentanyl analogues like isocarfentanil, lofentanil, sufentanil, & betahydroxyalphamethylfentanyl, as well as the piperazine based benzimidazole based nitazenes like metonitazene, isonitazene, N-pyrrolidino metonitazene and etonitazene lately & while it seems that Etonitazene is one of the strongest, the piperazine group causes extremely high anticholinergic effects, or some other receptor that causes dry mouth as it seems this is the effect that is way off the chart in relation to any other opiods . But aside from that, there seems to be a disconnect between the effect these drugs have on MOR and the effect that they have on Beta-arrestin-2. I believe when this disconnect occurs, the cell internalizes the MOR to downregulate & unless you administer the MOR antagonist or partial agonist quickly, the internalized MORs are not as naloxone /buprenorphine labile or susceptible. My results are anecdotal and as many of you who are aware of my history from Alt.Drugs.Hard and so on, As the Beta-Arrestin-2 Ki levels show higher binding affinity as well as Ki MOR levels going into pM and fM range. Carfentanil induced potent and extensive cell surface receptor loss, whilst the marked desensitisation of G protein-coupled inwardly rectifying potassium channel currents in the continued presence of carfentanil in neurones was prevented by a GRK2/3 inhibitor much more quickly than the other fentanyl derivatives, but when given time, the same thing happens, so it may be that some of these drugs are weaker GRK2/3 inhibitors in their own right. So my criticism of this study involves perhaps an autooxidation or reduction
MobiusDick
Here is a reference for you to look at and as soon as I feel better I will explain why I feel this way and possible changes to the study to confirm or disprove my suspicions