Nature Reviews Neuroscience has a fascinating article on drugs that remain dormant in the brain and only respond when damage occurs.
They’ve been christened pathologically activated therapeutic (PAT) drugs and rely on the fact that brain damage triggers specific chemical changes and drugs can be designed to take advantage of these processes.
For example, memantine is a type of drug that antagonises (blocks) the NMDA receptor which is activated by the neurotransmitter glutamate.
Important, because this receptor is known to be activated to excess in conditions like Alzheimer’s and Parkinson’s disease.
Several drugs block this receptor, including ketamine and PCP (‘Angel dust’), but they block the receptor as soon as they arrive.
Memantine is different – it doesn’t do its job unless the receptor has already been activated or ‘opened’ at least once already – making it a ‘non-competative antagonist’ – in other words, it doesn’t compete with the neurotransmitter, it waits until it’s been and gone.
It’s as if you wanted to prevent postmen from delivery their parcels by bricking up each door, but the householders will only open their door to the postmen.
So you hang around, wait for the postman to call, and then get in the doorway and block it. You’re not fighting the postmen while they deliver the letter, you’re avoiding conflict and taking advantage of what they already do.
This gives memantine a very important property. It blocks more receptors the more glutamate is about, or to return to our analogy, it can block more doors when there are more postmen about.
This means the drug ‘lies in wait’. As more NMDA receptors are activated owing to Alzheimer’s disease, the more it steps in to calm the situation down and prevent constant activation which is what is thought to cause the most damage.
The article outlines several other neurochemical processes that allow drugs to seemingly ‘lie in wait’ and only react to damage, rather than affecting the brain regardless of what else is happening.
It’s an interesting, clever and potentially very important twist on drug design that takes advantage of our growing knowledge of how the brain works in both illness and health.
Link to abstract of scientific paper.