title: The Pharmacology of Indomethacin.
abstract: BACKGROUND
  Over 50 years ago, indomethacin emerged as an extremely potent non-steroidal anti-inflammatory drug (NSAID) during a massive effort to find effective anti-inflammatory and analgesic medications. The 1960s saw acetic acid derivatives developed into indomethacin, diclofenac, and sulindac, and propionic derivatives into ibuprofen, naproxen, and ketoprofen. Indomethacin was likely the most potent of these compounds and one of the earliest to enter clinical trials. It is not surprising that indomethacin was among the first of the NSAID medications to be used in treatment of migraine and for headaches that eventually became known as "indomethacin-responsive" headache disorders. Potential pharmacokinetic and bio-mechanistic differences between indomethacin and other NSAIDs are of great clinical and research interest to explain this observation.
  
  
  RESULTS
  The present article summarizes pharmacologic properties of indomethacin, including pharmacokinetics with particular attention to its distribution into the central nervous system, adverse effects, drug interactions, and mechanisms of action. Data are emphasized where differences in biomechanisms are found between indomethacin and other NSAIDs. The use of indomethacin in pregnant and lactating women is reviewed.
  
  
  CONCLUSIONS
  NSAIDs easily enter the brain, but their high protein binding limits absolute amount of entry. All work similarly as either nonselective or selective cyclooxygenase inhibitors, but indomethacin may have more potent vasoconstrictive activity and unique direct neuronal or nitric oxide-dependent inhibitory pathway activity.
authors: Neurology & Neurological Surgery, Adjunct, Rehabilitation Medicine, University of Washington Medical Center, Harborview Medical Center, Seattle Concussion Clinic, Seattle, WA, USA.
authors: Sylvia
authors: S
authors: Lucas
mesh_terms: D000375:Aging / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000737:chemistry / Q000494:pharmacology*; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin
keywords: indomethacin; nonsteroidal anti-inflammatory drugs; prostaglandin inhibitors