Possibility to mask a charge to cross BBB, but metabolizes, so charge later prevents?

[Nagelfar]

Simple question. Can a charge on a particle be sustained, but masked in such a way, as to allow BBB penetration; but that metabolizes (possibly at a certain predictable interval after dosing) so that said charge prevents re-entry across BBB. (Perhaps to have only a quick effect, or as not to raise tolerance, or to be inactive shortly after making its intended effect; or so large doses don't accumulate their CNS effect, etc)?

 

[sekio]

This is one of the most poorly worded questions I have ever read, but yes, it is possible to have a molecule that becomes charged upon metabolism when it has crossed the BBB; MPPP+ and MPTP are the prime examples of this.

Other ways of "masking charges" could be e.g. conversion of carboxylate into esters, amides, carbamates, things like that.

 

[Nagelfar]

This is one of the most poorly worded questions I have ever read, but yes

heh.

How rapid is this process? Is it possible to have an extremely rapid effect, which clears the brain in a matter of minutes? (I'm thinking in relation to extremely potent drugs that would hit hard & fast with perhaps a mainline RoA)

 

[sekio]

I see what you're getting at, but it really depends on the structure of the drug in question. Some fentanyl analogues are rapidly destroyed by esterases - just like cocaine. Remifentanil is the one.