Phenacetin

Phenacetin is a non-opioid analgesic and antipyretic drug belonging to the acetanilide family, historically significant as the first major fever-reducing medication introduced to the market [1]. Its therapeutic action is primarily mediated through its conversion into paracetamol (acetaminophen), which inhibits cyclooxygenase (COX) enzymes in the central nervous system to reduce pain and fever [2]. Throughout the mid-20th century, it was frequently combined with aspirin and caffeine in popular 'APC' pain relief formulations [1]. However, phenacetin was banned or withdrawn in most countries by the 1980s following clear evidence linking its chronic use to analgesic nephropathy and various urothelial cancers [3]. The drug's mechanism involves elevating the pain threshold by acting on the sensory cortex and inhibiting prostaglandin synthesis [2]. Due to its significant toxicity profile, it is no longer used therapeutically but remains relevant in biomedical research as a selective metabolic probe for cytochrome P450 1A2 (CYP1A2) activity [2][4].

Other names

Acetophenetidinp-AcetophenetidideN-(4-ethoxyphenyl)acetamidePhenacetinum

Phenacetin acts as a prodrug to paracetamol, inhibiting cyclooxygenase enzymes (COX-1 and COX-2) in the central nervous system to reduce prostaglandin synthesis, while also acting directly on the sensory cortex to elevate the pain threshold [1][2].