In 1893, P-hydroxy-acetanilide was evaluated clinically by Dr. von Mering (1849-1908), who found that the drug produced methemoglobinemia.
Von Mering collaborated with the Bayer Company in a clinical trial of P-hydroxy-acetanilide, which it was postulated to be a metabolite of phenacetin by Trefuel and Hinsberg in1894.
He published a paper reporting on the clinical results of paracetamol with phenacetin, another aniline derivative. Von Mering claimed that, P-hydroxy-acetanilide to be effective antipyretic and analgesic, but believed it also had a tendency to produce methemoglobinemia.
Paracetamol was then quickly discarded in favor of phenacetin. It would remain, unused and apparently useless, for nearly half a century until it was rescued.
Von Mering's claims remained essentially unchallenged for half a century, until two teams of researchers from the United States analyzed the metabolism of acetanilide and paracetamol.
Paracetamol was reinvestigated half a century later by David Lester and Leon Greenberg from Yale University, who showed that it was indeed a metabolite of phenacetin in humans. In 1947 they found strong evidence that paracetamol was a major metabolite of acetanilide in human blood.
Lester and Greenberg demonstrated that paracetamol was the major metabolite so acetanilide and phenacetin and was relatively safe as an analgesic and antipyretic. In a subsequent study they reported that large doses of paracetamol given to albino rats did not cause methemoglobinemia.
Dr. von Mering and paracetamol
