How Pharmacology Learned to Aim

Morphine, first isolated in 1804, is an opiate found naturally in opium and acts as a mu-opioid receptor agonist in the central nervous system, the earliest drug on this trail to be purified from a natural source rather than compounded by hand.

Aspirin, first approved in 1897, is a nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase enzymes, the first stop on this trail synthesized rather than purified from a natural source, and the first whose action targets a named class of enzyme.

Arsphenamine, introduced at the beginning of the 1910s as the first effective treatment for syphilis, was toxic to Treponema pallidum, the bacterium that causes the disease, making it the first drug on this trail aimed at a specifically named pathogen rather than a general symptom.

Insulin, first approved in 1922, is a pharmaceutical protein hormone used to treat high blood glucose, the first stop on this trail that is itself the same molecule the body already makes, replacing a missing signal rather than blocking or purifying one.

Penicillin, first approved in 1928, is a beta-lactam antibiotic that inhibits penicillin-binding proteins and prevents bacterial cell wall formation, superseding arsphenamine-style organoarsenic treatment with a mechanism aimed at a structure bacteria alone possess.

Streptomycin, first approved in 1943, is an aminoglycoside antibiotic that binds the bacterial 30S ribosomal subunit and blocks protein synthesis, the first effective treatment for tuberculosis and this trail's first drug aimed at a bacterium's own protein-making machinery.

Chlorpromazine, first approved in 1953, is generally regarded as the first antipsychotic medication, used to treat schizophrenia and other psychotic disorders as a dopamine antagonist, the first stop on this trail aimed at a receptor in the brain rather than an infection or a hormone deficiency.

Warfarin, first approved in 1954, is an anticoagulant that blocks vitamin K epoxide reductase and reduces the body's clotting factors, the first stop on this trail aimed at a single named enzyme in a defined biochemical pathway rather than a receptor or a whole pathogen.

Sildenafil, first approved in 1998, is a phosphodiesterase type 5 inhibitor that blocks the breakdown of cyclic guanosine monophosphate to relax smooth muscle, developed for erectile dysfunction and pulmonary arterial hypertension and named on this trail for how narrowly its single named enzyme target is defined.

Oseltamivir, first approved in 1999, is a neuraminidase inhibitor that competitively blocks the influenza virus's own neuraminidase enzyme and prevents new virus particles from leaving an infected cell, closing this trail as a drug designed from the structure of a single viral enzyme rather than found by trial or purified from a natural source.