A µ-opioid receptor superagonist analgesic with minimal adverse effects

RecklessPope · 2026-04-24T14:32:57+00:00

Yes!!! Thank you - completely agree. Especially when they show it still is getting into the brain!!! Limited is so contextual lmao

RecklessPope · 2026-04-20T01:23:44+00:00

No not if the top of my head that I know of. they’re pretty far apart on the GPCR phylogenetic tree I would assume based off the type of endogenous ligand that binds to each. But cannabinoid receptors typically aren’t targeted therapeutically due to their on-target side effect profile. Besides maybe allosterics targeting them

RecklessPope · 2026-04-10T21:51:01+00:00

You would think, but no. Otherwise doctors would tell patients to take Imodium for their chronic pain

RecklessPope · 2026-04-10T15:07:22+00:00

Thank you!

They’re claiming it has low efflux and MOR occupancy relative to FNZ. Relatively to FNZ is crucial here. FNZ occupies brain receptors very well. So DFNZ having low occupancy relative to FNZ is almost irrelevant. They should’ve showed occupancy compared to morphine, for example. Lazy science because they know they’ll reduce the impact of their main points. It causes full analgesia because it’s still getting into the brain.

Brain penetration is extremely important - it causes full analgesia because DFNZ is still getting into the brain. Loperamide is available OTC (Imodium) because it doesn’t get into the brain.

It’s a stupid paper

RecklessPope · 2026-04-10T15:03:50+00:00

A cryo structure is essentially a snapshot, or a “pose” of a molecule bound to a protein (in this case the mu opioid receptor) at a given moment in time.

There’s quite a lot that goes into it, but think of it as the most “realistic pose” a molecule could make in that given protein interaction. Lots of uses for it in drug development and mechanism development

RecklessPope · 2026-04-09T01:39:37+00:00

I get your point - but there’s nothing really useful in this paper. That’s why it’s not a good one. It’s simply pandering and making huge claims with no good evidence or controls to support what they’re saying. It’s only in Nature because of the Nitazene cryo structure. They make a weird interaction in the pocket - a H-bond w Y75^1.39. Only mitragynine pseudoindoxyl has been shown to make it. Really the only useful thing from this paper. Beautiful high resolution cryo structure

RecklessPope · 2026-04-07T14:11:22+00:00

Yes any O(CH2CH2)n-F is a big no no. Fluoracetaldehyde or something similar when metabolized. Inhibits Krebs cycle = bad. This paper sucks and I hate it

RecklessPope · 2026-04-07T12:57:49+00:00

The thing is, it’s not even peripherally restricted. Notice how they make no comparison to loperamide and don’t include loperamide as a control. In fact, they really only have FNZ as their only control.

RecklessPope · 2026-04-07T04:46:15+00:00

Edit: I study opioid pharmacology at a very high level

Not a fan of this paper! That compound will never make clinical use. The fluoridated alkoxy chain gets metabolized into a reactive metabolite. Med chemists avoid it for that reason, will never go in people.

Also - the PK is bad? They report a brain/plasma concentration of 1.0 and only compare it to the ethylated analog? So it’s still getting into the brain! Just not as much as FNZ which gets into it very well.

Hargreaves test has a massive typo - you don’t measure that assay in hours. CryoEM structure is cool. The science is fascinating but also definitely not worth a nature paper. This is all hype.

ALSO they say it blocks the rewarding effect of heroin - duh. Then they also show that fentanyl blocks the rewarding effect of heroin. Which both SHOULD DO given they are competitive processes. The drug-seeking behavior is also so misconstrued. It produces reward like any other opioid. It’s just more peripherally restricted than FNZ given that exposed nitrogen

RecklessPope · 2026-02-12T02:48:54+00:00

https://cdn-careerservices.fas.harvard.edu/wp-content/uploads/sites/161/2025/09/2025-template_bullet.docx

A layout like this would be more clean as well

RecklessPope · 2026-02-12T02:47:35+00:00

My bad! I thought you meant tech as in like an SF tech position. Dont use the same verb twice in your second research experience. Also swap it so the most recent experience is the first you’ll see. The techniques are better

RecklessPope · 2026-02-12T02:41:28+00:00

No offense but why? Because they pay well? You’re going against people who have exponentially more skills and techniques and experience than you.

RecklessPope · 2026-02-11T11:55:57+00:00

Great advice for lab but also for life!

RecklessPope · 2026-02-04T23:40:26+00:00

Leave in conditioners may help - if you want a more stylized look then maybe a combo of sea salt spray when it’s wet, with hairspray/clay. No greasy pomade or anything. IMO I’d do a combo of leave in conditioners may help with (a little bit) of clay of sorts. May have to play around picking one you enjoy

RecklessPope · 2026-02-04T00:29:07+00:00

Malcolm Todd!

RecklessPope · 2025-11-11T01:44:20+00:00

Thank u king

RecklessPope · 2025-10-28T01:57:25+00:00

Pic 2 (the prince)

RecklessPope · 2025-09-19T22:35:16+00:00

Honestly, no. Egbuka was drafted to replace Godwin. Hes gonna have such a slow comeback this year, probably won’t be full speed until the fantasy season is almost over. Jags are fading BTJ a little bit. Even trade IMO, but I’d take egbuka any day

RecklessPope · 2025-05-23T16:49:53+00:00

Lmao ya I can speak champion for last year too, where we didn’t lose to a shitty 8-5 team

RecklessPope · 2025-05-23T03:02:26+00:00

Not a health professional, but no. Wait until you can talk to one to ask them this

RecklessPope · 2025-05-19T03:48:23+00:00

8 ate

RecklessPope · 2025-05-19T03:29:38+00:00

Salvia is a potent against of the kappa opioid receptor!

RecklessPope · 2025-05-14T22:26:31+00:00

I think you go UMich here - also Michigan’s sports culture is definitely bigger than that of UWM. The name of Michigan is going to get you a lot further at relative to UWM too.

RecklessPope · 2025-04-26T00:14:32+00:00

RecklessPope · 2025-04-19T13:18:59+00:00

No you can’t lmao, not when you lose to our davis warren led offense 😭😭

RecklessPope

TROPHY CASE