RM1490: A novel maintenance therapeutic for Opioid Use Disorder

[plumbus-nine]

Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the effects of high efficacy opioids and minimize opioid-cravings, while being safe and accessible to a diverse patient population. Although current OUD pharmacotherapies inhibit the euphoric effects of opioids of abuse, the extent to which they safely alleviate withdrawal and opioid-cravings, corresponds with their intrinsic µ opioid receptor (MOR) efficacy. The medium efficacy MOR agonist: buprenorphine in addition to inhibiting the euphoric effects of opioids of abuse, alleviates withdrawal and opioid-cravings, but its intrinsic MOR-efficacy is sufficient such that its utility is limited by abuse and safety liabilities. In contrast, although the MOR antagonist naltrexone minimizes euphoria and has no abuse liability, it exacerbates suffering associated with withdrawal and opioid-cravings. These observations indicate that a therapeutic with intrinsic MOR activity between the partial agonist (buprenorphine) and the antagonist (naltrexone) would strike a balance between the benefits and liabilities of these two therapeutics. To address this need, we derived RM1490, a MOR-agonist based on a non-morphinan scaffold, which exhibits approximately half the intrinsic MOR efficacy of buprenorphine. In a series of preclinical assays, we compared RM1490 to buprenorphine and naltrexone at doses that achieve therapeutic levels of occupancy of CNS MORs. RM1490 exhibited a behavioral profile consistent with reduced reward, dependence and precipitated withdrawal liabilities. RM1490 was also more effective than buprenorphine at reversing the respiratory depressant effects of fentanyl, and did not suppress respiration when combined with diazepam.

Significance Statement In preclinical our studies, RM1490 has a physiological and behavioral profile suitable for OUD maintenance therapy. (- Source -)

Doesn't sound too pleasurable and they always confuse that naltrexone is actually an inverse agonist but does anybody know the molecular structure of RM1490?

 

[Skorpio]

Looks like tapentadol. Got an imgur account just to post this.

Rms

 

[Tryptamite]

Tapentadol is shite. And very weak. Would only cover the smallest of habits.

Wonder is this stuff a full agonist? And if it blocks other opioid effects like bupe?

 

[plumbus-nine]

Wonder is this stuff a full agonist? And if it blocks other opioid effects like bupe?

It's half the potency of buprenorphine, so a weak partial agonist.

Had tapentadol when it was new and funnily for a short time the regulations were behind so it was sold as a RC ... back then I was opioid naive and liked it, but the NE component is strong and the opioid effects are weak.. O-DSMT is better probably.

 

[Tryptamite]

I imagine it has some potential as a pure powder and not an extended release pill. I kinda thought of it as half way from tramadol to morphine.

When I saw it for sale I confused it for ketobemidone and bought all the pills off the guy. I quickly realised my mistake lol.

 

[Nagelfar]

It's half the potency of buprenorphine, so a weak partial agonist.

Buprenorphine's strength of binding at its own target site is roughly 24× morphine - I suppose for a mixed-antagonist this scale of potency is regarded as simply 'functional' (or "weak" as you put it) - but I can't help concerning myself with what that would align to being were it a full agonist.

 

[Skorpio]

The compounds selling point is lower efficacy than buprenorphine, as to be less abusable.

Maybe this could better satiate cravings and not trigger folks but probably not especially recreational.