Aspirin: the first modern drug

Preparations derived from willow have been a regular feature of the human medicine cabinet for centuries: Ancient Egyptians drank willow ‘tea’ to relieve pain, and the Classic Greek physician Hippocrates wrote about the remedy in 400 BC. But it took a team of German chemists in 1897, working for Bayer, to synthesise a pure compound related to the active substances in willow, acetylsalicylic acid. They packaged it up neatly in pill form, and sold it under its trademarked name, Aspirin, which quickly became a household word.

Aspirin is arguably the first over-the-counter, modern drug. It was made via a defined chemical process, rather than isolated from a complex mixture, formulated in a portable, easy-to-ingest pill, and used to alter our elaborate chemical schemes.

Before Aspirin, chemists prescribed some ‘inorganic’ chemical molecules and numerous distillations, infusions and derivations of natural products. But the systematic, mass-produced and mass-marketed Aspirin was a game-changer.

How Aspirin works

Aspirin works mainly by half-mimicking a lipid (a half fat, half polar molecule) that gets converted by an enzyme into a signalling molecule – one of a (rather grandly named) family of prostaglandins. Prostaglandins have a huge range of functions and are found in most of our tissues.

Prostaglandin’s main job is to signal that inflammation is occurring in the body. When there is damage or inflammation, prostaglandin synthase enzymes (cyclooxygenases COX1 and COX2) are activated. They grab a rather ordinary lipid and convert it into a signalling molecule.

Aspirin looks enough like the polar part of that lipid to dive right into this enzyme. Aspirin donates an acetyl group to COX1’s protein, which puts a chemical spanner in its works, permanently stopping this enzyme’s function.

This is the major mechanism of Aspirin, and part of the reason why it blocks the sensation of pain, but the entire story of how it works is still a bit of a mystery.

While it’s permanently putting COX1 out of action, Aspirin is also inhibiting COX2 (reversibly) and preventing platelets from making thromboxane A2. That’s what keeps the platelets in blood less sticky, and why Aspirin is given to patients after heart surgery or stroke.

Indeed, it has been suggested that a regular low dose of Aspirin is just a general good once you are over a certain age.

Yes but why?

This uncertainty about a drug’s modes of action is more common than you might think. Certainly, for many of the earlier drugs, people had known for some time that they had some effect, but without understanding their molecular basis.

The precise mechanisms of action of many commonly prescribed drugs are still ambiguous. Many drugs – Aspirin included – seem to work precisely because they do more than one thing, making it even more complex to work out how these drugs work. In the modern era it is increasingly hard to get drugs without a precise mechanism of action through regulation.  However, over a century of precise use – and over a millennium of experimental use – has given us huge confidence in Aspirin’s utility as a medicine.

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