How do painkillers know where the pain is?

How do painkillers know where to go?
22 November 2022


painkiller pills



How do painkillers know where the pain is in my body? How does the pill know where it hurts?


Andrew - Yes. A very interesting question. You might imagine that pills must have some kind of destination board on the front saying, I'm headed for the liver, or I'm going to sort out that headache. But it ain't like that. Really the clue to this is in the fantastic discoveries that different molecules have got different shapes, different structures. Actually where we are in Cambridge is one of the great centers for discovering the structure of molecules. Originally, people used to look at the structure of rocks and minerals through shining x-rays and doing crystallography on them. And then people hit on the idea that we could do this with biological substances. If we could only make them into crystals, we could work out what the structure of these molecules is. And indeed the famous Nobel laureate, Dorothy Hodgkin's, work used x-rays, made crystals of penicillin and later on insulin, and discovered the precise structure and what that means, of course, just to make it clear, molecules are assemblies of atoms that are all bonded tightly to together, and they make an overall shape. And in the body, a huge number of molecules are very large, extremely large. They're called macromolecules. In fact, proteins are one example, DNAs another. And proteins are constructions of hundreds or often thousands of atoms into one gigantic molecule, which wraps up into a kind of globule. They're called globular proteins. And on the surface of these proteins, they have, and little hills and valleys and proteins in the body distributed often on the surface of different cells, have different shaped crevices and different shape hills and valleys. Now, when we take a drug, like a painkiller or any other drug, a beta blocker or a statin, these are small molecules, much, much smaller, and they've got a particular shape as well. So what happens when you take them, they course through the body, through the fluid systems, through the blood in particular bloodstream. And it's only when the shape of this little molecule happens to pass by a crevice or a little niche on a protein. And it fits, it's like a lock and a key. The drug molecule fits the crevice on a protein that it sticks. Basically the small molecules, the drugs and the medicine are passing by almost everything until it reaches a specific receptor. It's called a receptor because that's where it receives the drug.

Chris - A bit like triggering a landslide in your valleys discreetly in just the right valleys because the drug is addressed to the right parts of the body that have the right shape valley to happen

Andrew - I mean, I've emphasized shape there, but I should also for accuracy say that there's an electrical issue as well, that molecules have a, tend to have a positive end and a negative end, and they have to match up. So the positive end of a drug molecule matches up with a negative place on the receptor molecule

Chris - So there's a well known slogan for one brand that it hits pain where it hurts. Yeah. And so in some respects, that's not wrong. It's that the drug does kind of know where the problem is because the problem only exists where it hurts, so it binds to the right place. Absolutely. Andrew, thank you very much.


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