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Trevor Klee's avatar

I think this is pretty good!

I'd also say something about how some molecules, like dopamine, are evolutionarily conserved because they are broadly useful and very complicated. So, the dopamine in bananas is actually the same as the dopamine in our brains, and there's a fair bet that any tools bananas have to deal with their dopamine will also work on our dopamine.

Also, while caffeine, nicotine, and cocaine originally evolved to deter predation, the plants that produce them have evolved (and been selectively bred) now to encourage predation by humans. Being a useful plant to humans is a really successful evolutionary strategy. So, I think your point about "why don't plants evolve away" only works for that initial brief period that humans were detrimental to these plants' evolutionary success, like what supposedly happened with silphium.

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TheIdealHuman's avatar

Very interesting topic, there are many implications and questions about pharmacophilogenomy, both at how protein changes truly alter ligand binding (IMHO druggability via permutating variants of a known ligand is considerably simpler than reported, via post translation protein modifications, see e.g how almost all lead to relatively successful phenethylamine substitutes with relatively preserved TAAR1 agonism), the second being that similarly to how flowers or butterflies have emergently evolved to reproduce and maintain e.g. the shape of a face without any feedback from vision that many species have evolved drugs to bind stably to receptors they do not even express themselves (polyphenols, toxins, etc) this tend to argue that druggability is simpler than considered.

Anyway on a pedantic nitpick: ibuprofen main mechanism is not IIRC because of the inflammation caused by COX enzymes which is somewhat mild compared to cytokines but because COX is a key mediator of nociception

https://pubmed.ncbi.nlm.nih.gov/17071117/

IIRC ibuprofen is a major antalgic and a minor antiinflammatory drug (despite antipyretism)

(with off topic roles in the digestive system, and in vasodilation especially of the kidneys, btw other prostaglandins have understudied role in the brain and in chronobiotism)

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