Methadone vs Morphine

[chippermonk]

Chippermonk -- wait are you telling me a politician is a hypocrite? One in the Trump administration. Someone so considerate to people with things like autism. (ok ill stop)

Aren't they required to take the Hypocrite Oath in order to administer public health?

 

[Smyth2]

I'm physically handicapped so for me as a chemist I would happily supply spirodone over methadone since you get more doses per unit work.

Maybe a spirodone/loperamide analog since that is even less physical work to have to do.

Remember the amide doesn't necessarily mean it wouldn't pass the BBB since moramide is also an amide and strong analog of methadone.

I'm just exploring different ideas though, don't take it too religiously that I have actually attempted such work yet.

L-687,384 is not necessaily that easy to make though so if you had to go through all the steps it's for a superagonist not just skimping on the work load.

 

[Púca Rebellion]

"An intestinal obstruction is a blockage that prevents the normal flow of contents through the small or large intestine, often causing symptoms like pain, bloating, vomiting, and inability to pass gas or stool. It can result from various causes, including physical blockages, twisted intestines, or impacted stool."

I stand by what I said; as I lived it lol. Both these medications have caused me a lot of pain, and suffering. I was doing well on mono Buprenorphine, until they forced me to go off of it. I went back to street suply after that. We have virtually no options in the USA.

 

[Coffeeshroom]

Yes - levomethadone is some x20 more potent than dextromethadone. I know Germany now uses the more active enantiomer. It's crazy that other nations sill use raecemic methadone since it's been established that dextromethadone is cardiotoxic.

But for this comparison, I was assuming raecemic methadone (an equal amount of both enantiomers).

Yeah and the S.A version is a 50/50 mix of the 2 and there is also only one supplier having monopoly

 

[4DQSAR]

I'm physically handicapped so for me as a chemist I would happily supply spirodone over methadone since you get more doses per unit work.

Maybe a spirodone/loperamide analog since that is even less physical work to have to do.

Remember the amide doesn't necessarily mean it wouldn't pass the BBB since moramide is also an amide and strong analog of methadone.

I'm just exploring different ideas though, don't take it too religiously that I have actually attempted such work yet.

L-687,384 is not necessaily that easy to make though so if you had to go through all the steps it's for a superagonist not just skimping on the work load.

You realize that the extremely synthetically complex N-substituent does two things. It provides that PIF and it places an aromatic ring in an appropriate distance and orientation to said PIF. There are some other methadone derivatives that according to the limited research, manage that same feat without needing one to go thtough the dozen steps of producing a 3 ring system. I'm uncertain just how potent since they used values relative to pethidine... but yah, x1500 pethidine in 2 steps rather than 12.

 

[notsmokeymcpot42088]

Were you tryna hit a lick on the bupe clinic

They pissed me off to the point when I realized that I was the perceived threat --- I made damn sure they were late to wherever they were going next! If it were a metro area and not my clinic they just watched me leave and walk to my vehicle-- than of course not crime is bad. would have been about 15k in cash minimum surely. (Honestly they didnt hit the bank all week so x5). In a different life.

 

[notsmokeymcpot42088]

On the show : The Crime of the Century" a pain patient was offered a deal with the biggest Oxycotin rep of Florida that she would pay for the Rx if they could document him to show the drug was safe. He was prescribed 22-25qty Oxycotin 160mg every 12hrs for lower back pain. The guy saved the pill bottle to reference it later down the road,

I believe since Purdue was sponsoring the trial and the sales rep was bringing him the pills instead of filling at a pharmacy, that many of the OC 160mg pills were a placebo. If they were real his MME would be 6,000mg of morphine daily. The guy would have been dead 100%

I gotta see that show! Way off topic but a friend was over telling me there kid found a book called "The incredible journey of Baron Trump" written in the 40's-50's about someone named baron trump who is a time traveler who claims in his time his father donald was the president. (Coincidence, surely?) Noone pay attention to that unless you want to.

160 x 25 oly wa -- even if some were placebos that is an oohhh dammnn forsure.

Chippermonk - I have a song about how EVERYONE is on drugs and the last bar is "thats the hypocratic oath from our hypocritic players" -- its called "everyone is on drugs" (Cuz I am super creative)

 

[Them Witches]

I gotta see that show! Way off topic but a friend was over telling me there kid found a book called "The incredible journey of Baron Trump" written in the 40's-50's about someone named baron trump who is a time traveler who claims in his time his father donald was the president. (Coincidence, surely?) Noone pay attention to that unless you want to.

160 x 25 oly wa -- even if some were placebos that is an oohhh dammnn forsure.

Chippermonk - I have a song about how EVERYONE is on drugs and the last bar is "thats the hypocratic oath from our hypocritic players" -- its called "everyone is on drugs" (Cuz I am super creative)

OC 160mg every 12 hours take 22-25 pills... what a nightmare of a habit ? The guy was saying he was still in pain taking 12qty 160mg every 12hrs...

 

[notsmokeymcpot42088]

For real --- could you imagine catchin an 160mg placebo, I feel like I would note that real quick. (not complain and take another) lol. Still in pain -- Damn! I imagine once tolerance sets in that could happen but WOW if that isnt doing it idk what would. Couple grams of oxycodone a day at that point "Save the pills just give me baggies please". Purdue really did alot of ppl dirty --- not as bad as acetemenophin(sp) but still

My (very lame) real life example is I am in my late 30s and afaik don't have any pain --- get a little sick from sub and all of a sudden I got a bad back and knee. (wtf lol).

 

[Them Witches]

I gotta see that show! Way off topic but a friend was over telling me there kid found a book called "The incredible journey of Baron Trump" written in the 40's-50's about someone named baron trump who is a time traveler who claims in his time his father donald was the president. (Coincidence, surely?) Noone pay attention to that unless you want to.

160 x 25 oly wa -- even if some were placebos that is an oohhh dammnn forsure.

Chippermonk - I have a song about how EVERYONE is on drugs and the last bar is "thats the hypocratic oath from our hypocritic players" -- its called "everyone is on drugs" (Cuz I am super creative)

HBO's mini series -- It can be viewed by streaming MAX or HBO
The Crime of the Century -- 2021 -- Season 1 // episodes 1 & 2

 

[Them Witches]

For real --- could you imagine catchin an 160mg placebo, I feel like I would note that real quick. (not complain and take another) lol. Still in pain -- Damn! I imagine once tolerance sets in that could happen but WOW if that isnt doing it idk what would. Couple grams of oxycodone a day at that point "Save the pills just give me baggies please". Purdue really did alot of ppl dirty --- not as bad as acetemenophin(sp) but still

My (very lame) real life example is I am in my late 30s and afaik don't have any pain --- get a little sick from sub and all of a sudden I got a bad back and knee. (wtf lol).

My bad it was more than 6,000 MME. 160mg X 50qty per day equals 8,000mg of Oxycodone, that is a 12,000 MME lol... The man would be dead so there must have been a great percentage of placebo in that Rx. Medical data states that 2,000 MME is the top of the chart "ultra high MME"

The guy with the laughable " 5 digit MME " of 12,000 would be like him wearing 66qty Fentanyl 100mcg patches at all times OR taking 360-400qty Methadone 10mg tablets daily OR taking 375qty Hydromorphone 8mg daily OR taking 267qty Roxicodone 30mg daily... Imagine someone taking 17qty Roxicodone 30mg every hour and still sleeping 8hrs per day... ???

Filling a 30 day Rx for 11,250qty Hydromorphone 8mg OR a 30 day Rx for 8,010qty Roxi 30's... There isn't a pharmacy on this planet allowed to order that much by the DEA for only one patient/customer. The pharmacy would have to order 80qty stock bottles of 100ct per stock bottle per month for him. The DEA would have shut that down quickly. And at what point in time does any company producing schedule II narcotics admit to starting and completing a trial experiment at that level.

Again for the record, the man did not have extreme cancer pain. It was lower back pain. Those Oxycotin CEO's used the man to fake medical usage documents to con the world into thinking the drug is absolutely A-Okay even at "5 diget MME scores"...

The man said quote, "I was starting to feel toxic..." lol. Well no shit, his liver, kidneys, stomach, intestines, and other organs would have shut down quicker than melting a stick of butter in a bonfire. That much Oxycodone would be like eating rat poison by the plate full because that is what toxic doses of Thebaine is compared to.

 

[4DQSAR]

There do exist people for whom opioids do not work. But I presume that even in such people, oxycodone will become toxic in other ways at sufficintly high doses. So OK, myabe you find someone for oxycodone doesn't work and is also blessed with a metabolism that protects from the toxicity...

But then you have ONE patient. Not statistically valid.

That said, amazed by how little Perdue reps actually knew about medicines. Their job was to sell medicines, not understand let alone be able to explain HOW they work.

 

[Them Witches]

There do exist people for whom opioids do not work. But I presume that even in such people, oxycodone will become toxic in other ways at sufficintly high doses. So OK, myabe you find someone for oxycodone doesn't work and is also blessed with a metabolism that protects from the toxicity...

But then you have ONE patient. Not statistically valid.

That said, amazed by how little Perdue reps actually knew about medicines. Their job was to sell medicines, not understand let alone be able to explain HOW they work.

Yes indeed.

8,000mg of Oxycotin per day is not having enough sense to stand up in a mud puddle

 

[Smyth2]

I was on the computer just now and came accross this loperamide-aripiprazole hybrid:

4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide

4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide | C28H31Cl2N3O | CID 164916972 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Bonifazi A, Battiti FO, Sanchez J, Zaidi SA, Bow E, Makarova M, Cao J, Shaik AB, Sulima A, Rice KC, Katritch V, Canals M, Lane JR, Newman AH. Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management. J Med Chem. 2021 Jun 10;64(11):7778-7808. doi: 10.1021/acs.jmedchem.1c00611. Epub 2021 May 20. PMID: 34011153; PMCID: PMC9308496.

WO2022187206A1 - Dual-target mu opioid and dopamine d3 receptors ligands; preparation and use thereof - Google Patents

Disclosed herein are novel dual-target compounds that bind at both the mu-opioid receptor (MOR) and dopamine D3 receptors (D3R) to provide MOR-mediated analgesia, while minimizing addictive liability through D3R antagonism/partial agonism. The novel compounds are useful in the treatment of pain...

patents.google.com

 

[Smyth2]

 

[Smyth2]

It's called AB06-117 (23).

Novel Dual-Target Mu Opioid (MOR) and Dopamine D3 Receptors (D3R) Ligands as Potential Non-Addictive Pharmacotherapeutics for Pain Management - PMC

The need for safer pain-management therapies with decreased abuse liability inspired a novel drug design that retains μ-opioid receptor (MOR)-mediated analgesia, while minimizing addictive liability. We recently demonstrated that targeting dopamine ...

pmc.ncbi.nlm.nih.gov

 

[Smyth2]

With the longoperidol (Penfluridol) amine you get something called fluperamide.

If you can get fluperamide this is meant to be better than loperamide for crossing the bbb.

 

[Conky]

The thing is, buprenorphine and naloxone have roughly the same receptor affinity. I haven't checked if one has a significnatly lower EC50 than the other but my suspicion is that the values will be similar.

Long ago I talked to a French BLer who mentioned that they would fix buprenorphine + naloxone tablets. They remarked that they would feel ill for around 10 minutes until the extremely short T1/2 of naloxone meant that the buprenorphine took over.

Actually, AFAIK it's a lie that consuming a full agonist after buprenorphine will produce withdrawal. Yes, suficient buprenorphine will blunt the effects of a full agonist, but it won't produce WD.

On the plus side, I found that just 4mg buprenorphine/day (the most I could tolerate) was sufficient to essentially reverse my dependence. I only took it for a week and ignored the dictum that 'however much a client consumes, ALL clients will slowly be titrated up to 16 or 24mg/day and then a reduction from there' which was to me a HUGE dose. I just didn't need it and given the severe anxiety, didn't WANT it. It certainly made me think 'I never want to NEED that stuff again' and 15 years later, the only drugs I consume are those prescribed to me. I seek nothing safe pain relief.

And do they prescribe testosterone to male patients on 16 or 24mg bupe? 24mg will reduce test levels significantly. Could even end up with <10nmol total test.

 

[4DQSAR]

With the longoperidol (Penfluridol) amine you get something called fluperamide.

If you can get fluperamide this is meant to be better than loperamide for crossing the bbb.

I don't think loperamide has much trouble crossing the BBB. I think it's the fact that it's a substrate for the ATP-binding cassette that's the important thing.

That's why it's so dangerous. It displays a 2-phase dose/response curve. On Opiophile people were eating 200mg of loperamide a day to stop WD but when they increased that doses to 250mg, some ended up in hospital and some died. As soon as the dose overwhelms the transports, it STAYS in the brain.

That's just my opinion - I've studied all of the formal documents and found as many personal communications as possible but for a long, long time I have been concerned about how loperamide was (is?) being (ab)used in the US.

 

[daturetard]

I was on the computer just now and came accross this loperamide-aripiprazole hybrid:

4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide

4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide | C28H31Cl2N3O | CID 164916972 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more.

pubchem.ncbi.nlm.nih.gov

Bonifazi A, Battiti FO, Sanchez J, Zaidi SA, Bow E, Makarova M, Cao J, Shaik AB, Sulima A, Rice KC, Katritch V, Canals M, Lane JR, Newman AH. Novel Dual-Target μ-Opioid Receptor and Dopamine D3 Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management. J Med Chem. 2021 Jun 10;64(11):7778-7808. doi: 10.1021/acs.jmedchem.1c00611. Epub 2021 May 20. PMID: 34011153; PMCID: PMC9308496.

WO2022187206A1 - Dual-target mu opioid and dopamine d3 receptors ligands; preparation and use thereof - Google Patents

Disclosed herein are novel dual-target compounds that bind at both the mu-opioid receptor (MOR) and dopamine D3 receptors (D3R) to provide MOR-mediated analgesia, while minimizing addictive liability through D3R antagonism/partial agonism. The novel compounds are useful in the treatment of pain...

patents.google.com

Man wouldn't the d2 antagonist properties
Take all the fun out of it though? An antidiahreal antipsychotic just sounds like they're trying to get APs stopping even MORE biological functions. Idk though I don't fuck around with APs.
You guys seen them studies on long term AP use and brain atrophy?