antagonist and agonists conversion?

[fluxy]

I have been wondering for a while now, how exactly one can calculate how much of an agonist opiate like morphine oxy etc is required to "jump" or get stoned if you have a certain level of an opiate antagonist in your system such as naltrexone or more importantly buprenorphine. Is there Any conversion ratio or is it just people and there own bodies?

one thing that troubles me is that say, you only need 0.5 to 2mg of naloxone to reverse say a decent shot of heroin, for example 200mg. but if you have only taken 2mg of buprenorphine, that same 200mg shot of heroin would jump it and get you high. and the same with say only 500 microgrammes of fentanyl. its very confusing? Can anyone tell me how antagonists do there work as the mathematics just doesnt make sense. I Can picture antagonists running thru the bloodstreams knocking opiates off there receptors, hmmm maybe its more complicated than that.

In my experience, anything over 8mg of buprenorphine in your system in the last 12 hours and your wasting your gear or oxy unless you have a lot, although it wont get you high, it will reverse withdrawal symptoms.

any links or article links would be appreciated thanks,

fluxy

 

[Bob Loblaw]

Coincidentally, I read a nice article about agonists and antagonists earlier today.

Agonist

An agonist is a mimetic of the natural ligand and produces a similar biological effect as the natural ligand when it binds to the receptor. It binds at the same binding site, and leads, in the absence of the natural ligand, to either a full or partial response. In the latter case, it is called a partial agonist. The figure below shows the action of ligand, agonist, and partial agonist.

There is another kind of agonist, given the bizarre name inverse agonist. This term only makes sense (to me) when applied to a receptor that has a basal (or constituitive) activity in the absence of a bound ligand. If either the natural ligand or an agonist binds to the receptor site, the basal activity is increased. If however, an inverse agonists binds, the activity is decreased. An example of an inverse agonist (which we will discuss later) is the binding of the drug Ro15-4513 to the GABA receptor, which also binds benzodiazepines such as valium. When occupied by its natural ligand, GABA, the protein receptor is "activated" to become a channel allowing the inward flow of Cl- into a neural cell, inhibiting neuron activation. Valium potentiates the effect of GABA, which is enhanced even further in the presence of ethanol. Ro15-4513 binds to the benzodiazepine site, which leads to the opposite effect of valium, the inhibition of the receptor bound activity - a chloride channel.

* inverse agonists: a good explanation
For our purposes, just concentrate on the agonist and partial agonist.


Antagonists

As there name implies, antagonist inhibit the effects of the natural ligand (hormone, neurotransmitter), agonist, partial agonist, and even inverse agonists (which will not be mentioned again). We can think of them as inhibitors of receptor activity, much as we considered in the sections above inhibitors of enzyme activity. As such, there can be different types of antagonists. These include:

* competitive antagonist, which are drugs that bind to the same site as the natural ligand, agonists, or partial agonist, and inhibit their effects. They would be analogous to competitive inhibitors of enzyme. One could also imagine a scenario in which an "allosteric" antagonist binds to an allosteric site on the receptor, inducing a conformational change in the receptor so the ligand, agonist, or partial agonist could not bind.
* noncompetitive antagonist (or perhaps more generally mixed antagonist) which are drugs that bind to a different site on the receptor than the natural ligand, agonist, or partial agonist, and inhibit the biological function of the receptor. In analogy to noncompetitve and mixed enzyme inhibitors, the noncompetitive antagonist may change the apparent KD for the ligand, agonist, or partial agonist (the ligand concentration required to achieve half-maximal biological effects), but will change the maximal response to the ligand (as mixed inhibitors change the apparent Vmax. The figure below shows the action of a competitive and noncompetitive antagonist.
* irreversible agonist, which arises from covalent modification of the receptor.



http://employees.csbsju.edu/hjakubowski/classes/ch331/transkinetics/olinhibition.html

That clear things up?


TL;DR Agonists fit into a receptor site and make the receptor fire.
Antagonists fit into the receptor site with greater 'force' than an agonist, thus inhibiting the agonist from causing the receptor to fire anything. The antagonist can partially inhibit of ully inhibit depending on its type. Additionally, the antagonist may attach to a separate receptor site and prevent agonist effects from there.

 

[Too many doses]

^good post thank you .

 

[Bob Loblaw]

No problem Sorry I couldn't help you with the dosages needed though. If you have any more basic questions, feel free to ask.