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how do some opiates have a higher affinity for opiate receptors than others?

K

KeepMeAlivePls

Greenlighter
Joined
Jun 5, 2009
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This might sound insane to some because its not your conventional opiate habbit. I love opiates and I can't afford to cop heroin every day, so I chose suboxone as my DOC. I've been doing it for about 3 months on a daily basis, a quarter still gives me a nice, long high. Street price over here is around $10 per pill. So if I only do a quarter a day $10 can last me 4 days.

Anyways.......

I decided to ask this question because I simply don't understand how some opiates have a higher affinity than others. Doesn't make sense to me, I understand the concept and all but what determines how strong it binds to your receptors? Does it have to do with molecular structure?

I have another question on this topic only this time specifically regarding buprenorphine. When I snort suboxone I don't feel any effects until 45 min to an hour later. Is this because the naloxone competes for the receptors? Will you feel effects instantly if you snorted subutex (pure buprenorphine + filler)?

Thanks.
 
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KeepMeAlivePls said:
...Does it have to do with molecular structure?
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Yes. That's pretty much the only thing it has to do with.

I have another question on this topic only this time specifically regarding buprenorphine. When I snort suboxone I don't feel any effects until 45 min to an hour later. Is this because the naloxone competes for the receptors? Will you feel effects instantly if you snorted subutex (pure buprenorphine + filler)?

Thanks.
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The naloxone is actually not strong enough to really compete with buprenorphine, also it is very poorly absorbed unless you IV.

That's just the way bupe is, if you snorted subutex it would come on slow also. Even when you IV them they come on slow.
 
It's not about how strong they bind to the receptor.

It's about how easily it binds to the receptor. Do some research on what a GPCR is really like, and what a binding site is. You should quickly realize that the easier a ligand can reach the binding site and assume the correct configuration (molecules are generally not perfectly stiff, they wiggle around, some more easily than others). Fentanyl can wiggle a lot, and morphine not so much, but fentanyl can easily assume the correct shape that will bend the receptor into the correct configuration needed to stimulate it.
 
That has absolutely nothing to do with affinity. Methadone and hydrocodone are about as potent as eachother, at least in acute dosing, but their half lives are way, way different.

That has to do with how the drug is metabolised, how lipid soluble it is (if it can build up in body fat, the liver).

Affinity has to do with the actual shape of the molecule as it comes into contact with the receptor protein. Other issues are relevant in vivo, but this is the real key for in vitro studies which is what you'll usually see in a study.
 
A good illustration of hammy's point: isn't LSD a partial agonist at 5ht2a?
edit: I'm wrong, nvm. I was conflating binding affinity with propensity to activate the receptor.
 
Hammilton said:
Methadone and hydrocodone are about as potent as eachother, at least in acute dosing...
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Not to derail the thread, but that's definitely off.

I have a pretty huge tolerance to opiates, (at my peak I was doing 4 OC80s a day), and although I don't really use anymore I can *feel* a 40mg wafer. It doesn't get me high really, but I'll feel pretty nice through out the day. However, I don't take it every day, let alone every month.

I guarantee you I wouldn't feel 40mg of hydrocodone.

Also, when I was starting out with opies, a 10mg methadose would almost make me puke but 35mg of hydrocodone would get me niiiiice.

Methadone is definitely more potent than hydrocodone, regardless of halflife.
 
the difference b/w what u r saying and what hammilton is saying is that he is basing his answers on actual studies and chemistry behind it and u r basing it on subjective experience.

Very different thing those are.
 
N0 W4RN1NG said:
Not to derail the thread, but that's definitely off.

I have a pretty huge tolerance to opiates, (at my peak I was doing 4 OC80s a day), and although I don't really use anymore I can *feel* a 40mg wafer. It doesn't get me high really, but I'll feel pretty nice through out the day. However, I don't take it every day, let alone every month.

I guarantee you I wouldn't feel 40mg of hydrocodone.

Also, when I was starting out with opies, a 10mg methadose would almost make me puke but 35mg of hydrocodone would get me niiiiice.

Methadone is definitely more potent than hydrocodone, regardless of halflife.
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You can't determine potency of drug when tolerance is involved. Tolerance of a drug varies depending on the pharmacology behind it. Your subjective experiences mean nothing in this case.
 
Agreed, however, when I had no tolerance, 10mg of methadone was if anything a bit stronger than 35mg of hydrocodone,as I pointed out in my last post.

And I know I'm not the only one who feels that way, I guarantee all of my friends who indulge would agree that methadone is definitely more potent, acutely and chronically, than hydrocodone.

You give any opiate-virgin 20mg of methadone and there's a really fucking good chance that motherfucker will be in sorry shape.

You give 'em 20mg of hydrocodone and they'll have a light buzz.
 
Studies don't agree with that. At least none that I'm aware of, though I admit it's been a long time since I took look, and the subject has always been murky with some papers contradicting others.
 
It is possible that a substance is more potent in overall central effects, but less potent in producing recreational effects (euphoria etc.)

Thus, when evaluated scientificly, in bioassays, animal testing etc. the compound would seem more potent, but in recreational use, it would seem less potent, because the effects that are sought after in either setting are different.
 
Equivalent doses for methadone are varied depending on the source or study. It is somewhat unique. On paper it has analgesic properties similar in potency to hydrocodone.

Subjectively, i find methadone to be more "potent" than hydrocodone. 40mg would methadone would produce an overall subjective high greater than 40mg of hydrocodone, but the hydrocodone would come on quick and with some strength.

But again, methadone has some distinct differences in both pharmacodynamics and pharmacokinetics; it is hard to compare....
 
Equivalent doses for methadone are varied depending on the source or study. It is somewhat unique. On paper it has analgesic properties similar in potency to hydrocodone.

Subjectively, i find methadone to be more "potent" than hydrocodone. 40mg would methadone would produce an overall subjective high greater than 40mg of hydrocodone, but the hydrocodone would come on quick and with some strength.

But again, methadone has some distinct differences in both pharmacodynamics and pharmacokinetics; it is hard to compare....

I have seen people be sick for days (vomiting) from taking just 20mg of methadone, yet are able to take larger amounts of hydrocodone without issue....

A friend of mine once stole 4-5 10mg methadone tablets from my stash (who had experience with hydrocodone and oxycodone but was not tolerant), and then took them all. I had previously warned him to only take one. He took them all, and was vomiting and incapacitated for quite some time....

Personally, I can tolerate 50-60mg of methadone with zero tolerance, but a number of years ago I was on MMT at doses far higher than that, so I may have somewhat of a permanent tolerance. Anything above 60mg without a tolerance (for me) is uncomfortable territory that will require me to sit very still in order to avoid getting sick. My guess is that with zero tolerance it would take (me) 180-200mg of methadone to induce a fatal overdose. Some sensitive non-tolerant individuals could potentially die from as little as 40-50mg of methadone. Most non-tolerant people would survive 50mg of hydrocodone without the aid of an antagonist....
 
I have no formal education in the matter but am in the understanding that much of a drug's potency has to do with how quickly it can cross the blood brain barrier: i.e. lipid solubility. For instance diacetylmorphine crosses the BBB faster than morphine because the two acetyl groups allow for greater lipid solubility- hence the more complete high.
 
crossing the blood brain barrier more easily will perhaps give you the "more complete high" in the acetylmorphine/morphine case you mentioned, but that is caused by a higher effective concentration of acetylmorphine crossing over (it is thus more "bioavailable"). So if more substance can get into the brain, it will have a greater effect (all other things being equal). This doesn't have anything to do with receptor binding really.

To address the original question, I like this crude analogy: imagine you have an opiate receptor that is shaped like a shoe (say size 10 US and left footed). You are trying to fit several different foot-shaped opiates into this "shoe-receptor". Some of your opiates are size 9, some are size 11+, some are right feet, some are left feet, some have missing toes, some have extra toes etc. (and they are all in the process of wiggling whatever toes they might have :) )

They all "fit" to varying degrees. But they are also being destroyed/metabolized/excreted, so there is a "race" to fit into as many "shoe-receptors" before this happens. The best fit, will win the race :)

Feel free to make fun of my analogy if you must :) (I'm a chemist, not a biologist, so please excuse me) It was fun to write it up.

The perceived effects will not be exclusively a matter of how well a substance binds a receptor, but also factors like bioavailability, rate of metabolic destruction (half-life), individual biology are important.
 
What aspect of buprenorphine's architecture gives it so powerful a mu affinity? Can we use this structural aspect to synth a full agonist with buprenorphine's potency--a full agonist that buprenorphine will not extirpate?
 
^ Extremely obvious answer - no, you can't, because it's already been studied extensively, and the answer could be found via a simple wikipedia search. And besides, there are all sorts of full agonists that are as potent and more potent than buprenorphine. It's potent, but it's miles away from being "highly potent".

If you looked, you'd see that buprenorphine is a dihydroetorphine derivative, so it's really obvious what to do to get a potent full agonist. Pretty much what you do with any phenanthrene opioid- you get rid of the n-cyclopropylmethyl group and replace it with a n-phenethyl group. Or N-ethyl or N-ethyl. You go from partial agonist or antagonist to full agonist. This is actually really basic, there are dozens of papers that
 
i agree

N0 W4RN1NG said:
Agreed, however, when I had no tolerance, 10mg of methadone was if anything a bit stronger than 35mg of hydrocodone,as I pointed out in my last post.

And I know I'm not the only one who feels that way, I guarantee all of my friends who indulge would agree that methadone is definitely more potent, acutely and chronically, than hydrocodone.

You give any opiate-virgin 20mg of methadone and there's a really fucking good chance that motherfucker will be in sorry shape.

You give 'em 20mg of hydrocodone and they'll have a light buzz.
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i agree with homeboy, ive been a pillhead for like 3 years now and i feel the same way he does 20 mg of methadone is deff stronger then 20 mg of oxys
methadone and suboxone are used to kick herion addictions and herion is definatley stronger than oxys, i kno this bc ive abused herion oxys methadone and suboxone all at dif times
 
Hammilton, that's not what I meant. I mean what is it about buprenorphine that allows it to extirpate most other opiates.

I swear I'll never use the P word again.

Wait...what extirpates bupe?

edit: never mind. I see what you mean. Thanks.
 
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