What determines dosage?

[alf meneas]

I realise this may not be the appropriate forum, but I've not explored too far round the other rooms...

What is it about a given compound that determines the dosage range?
Some things are active in tens of micrograms, some you're talking happily absorbing tens of milligrams.
I'm familiar with the idea of 'response curve' and 'therapeutic index', but I guess that is a separate matter.
It is also something I'm curious about though - why would twice as much of substance x be equivalent to twice as much in one case, and ten times as much in the case of substance y?

This may well be a pharmacology question I'm not educated enough to get an answer to, or one I should be asking elsewhere or looking up for myself, but it seemed to me that there'd be a few heads here who'd have something interesting to say.

 

[.:Holy::Toast:.]

Bioavailability could be seen as one determining factor, although the change in dosage it can cause is mostly negligible when discussing the broad range of dosages you speak of (a hundred or less ug for threshold NBOMe dosage versus a couple mg for threshold psilocin dosage)
If I'm not mistaken the main determining factor in dosage has to do with the binding affinity for these psychedelic substances to the 5-HT receptors they act upon.
Take NBOMe for example, they have a high binding affinity for the receptors they act upon, however even that is not a perfect explanation.
Other factors I don't REALLY understand like possibly metabolism may be taken in to play as well because binding affinity does not always correspond to the observed dosage for a substance.
Perhaps some substances have the ability to repeatedly stimulate receptors or to stimulate receptors more often than others but this does not necessarily need to correlate to the binding affinity values.

 

[perpetualdawn]

Someone is going to pipe in and be able to give a better answer than me, but here's how I look at it, pretty simplified I think:

You're familiar with the lock and key analogy of neuroreceptors and neurotransmitters/drugs? Basically, some compounds fit into the receptors much better than others. You can think of the receptors as kind of mushy key holes, kind of like tiny, oddly shaped vaginas. I like to think of a sexual analogy, little odd shaped vaginas and little odd shaped penis'. Some "keys" have just the right shape and slide in perfectly, others don't fit so well. Some keys fit in partially, but still do a really good job of tickling the receptor, but they get "knocked out" of the receptor easily. Others will fit in really well, and also tickle well. Others will fit in well, and not stimulate the receptor at all... etc.

The keys that fit in well, and do a very effective job of stimulating the receptor are called "agonists".

They keys that fit in well, but don't stimulate the receptor much are called "antagonists".

There are also "partial agonists", "partial antagonists", and some other classifications.

Another factor is how readily the drug is broken down by enzymes in your body. Some drugs get broken down more efficiently by our bodies than others. This affects the length of the experience, as well as the intensity.

Another factor is how easily a drug can get out of your bloodstream, and into your neural tissues, aka crossing the blood-brain-barrier. Our bodies have mechanisms to prevent many chemicals from crossing out of the blood stream and into our synapses. This helps our brain maintain stable conditions.

Another factor: sometimes when one drug gets broken down by the bodies enzymes, it produces another psychoactive drug. An example of this is psilocybin to psilocin. The rate at which this happens, vs. the rate the second step (psilocin) gets broken down will affect potency.

How does the exponential curve happen? I'm not really sure. It could be that at certain levels, the enzymes that are responsible for breaking the chems down get used up, so the drug becomes more effective. This probably happens with mescaline, and is related to how ayahuasca works (vis a vis MAO inhibitors)..

Anyways, that's my cartoon view of some neurochemistry. I'm really amateur, so anyone with a more advanced understanding, please correct any mistakes here.

 

[ParappaTheRapper]

the size of your penis. Jk.