Prescribed as the racemate. Both enantiomers inhibit serotonin reuptake with broadly similar potency, so unlike escitalopram there is no single-enantiomer version worth marketing. They differ downstream: S-norfluoxetine, the metabolite, is the long-lived active one and is why fluoxetine takes weeks to clear.
Molloy, with Klaus Schmiegel and Kenneth Hauser, synthesised the phenoxyphenylpropylamine series from which fluoxetine came; the most potent serotonin-uptake inhibitor in David Wong's screen was the oxalate LY82816, and Molloy and Hauser then made the more soluble hydrochloride, LY110140, which is fluoxetine. Ray Fuller chaired the project team. First published in Life Sciences in 1974 (Wong, Horng, Bymaster, Hauser, Molloy); composition-of-matter patent US 4,314,081 to Molloy and Schmiegel, filed 10 January 1974. FDA approval 29 December 1987, launched as Prozac January 1988. It was the first SSRI marketed in the United States and the first commercially successful one, but not the first SSRI to market: Astra's zimelidine reached European markets in 1982 and was withdrawn.
Wong proposed re-testing the Molloy/Schmiegel series for serotonin, norepinephrine and dopamine uptake; the assay that singled out LY-110140 was run in his group by Jong-Sir Horng in May 1972 and published in 1974 (Wong, Horng, Bymaster, Hauser, Molloy). He did not synthesise the compound — that was Molloy and Schmiegel — and the team is normally given as four, with Ray Fuller confirming the result in his p-chloroamphetamine rat model.
