Prostaglandin-endoperoxide synthase 1 variant (Cyclooxygenase-3) (COX-3)

Cyclooxygenase-3 (COX-3) is a splice variant of the Prostaglandin-endoperoxide synthase 1 (COX-1) enzyme, encoded by the PTGS1 gene. It is predominantly expressed within the central nervous system (CNS), including the cerebral cortex and spinal cord, where it plays a critical role in the synthesis of prostaglandins that mediate pain and fever [1.2.1, 1.2.3]. COX-3 was identified as the putative target for acetaminophen (paracetamol), explaining why the drug provides central analgesic and antipyretic effects without the significant peripheral anti-inflammatory activity or gastrointestinal toxicity associated with traditional NSAIDs [1.4.1, 1.4.5]. Although its existence as a functional protein in humans is debated due to a frameshift in the human mRNA transcript, the enzyme remains a key pharmacological concept for drugs that selectively inhibit CNS prostaglandin production [1.2.2, 1.4.4]. In addition to acetaminophen, other drugs such as dipyrone and phenacetin are known to interact with this target [1.4.1]. Understanding COX-3 is essential for developing analgesics that target central pain pathways while sparing peripheral homeostatic functions [1.2.4, 1.3.3].

Other names

COX-3Cyclooxygenase-3COX-1 variant 1PTGS1 variantPCOX-1a

Inhibition of the cyclooxygenase activity of the COX-1 splice variant in the central nervous system, reducing the production of pro-pyretic and pro-nociceptive prostaglandins like PGE2.