, Volume 33, Issue 4, pp 224–234 | Cite as

Different Mechanisms in Formation and Prevention of Indomethacin-induced Gastric Ulcers

  • Halis SuleymanEmail author
  • Abdulmecit Albayrak
  • Mehmet Bilici
  • Elif Cadirci
  • Zekai Halici


Indomethacin is an indol derivative, non-steroidal, anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. Indomethacin became the first-choice drug to produce an experimental ulcer model as a result of having a higher ulcerogenic potential than other non-steroidal anti-inflammatory drugs (NSAIDs). There have been several conflicting reports about the ulcerogenic mechanism of indomethacin; the mechanism is still unclear. It has been suggested that indomethacin induces gastric damage via inhibiting the release of protective factors like cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2), bicarbonate, and mucus; increasing aggressive factors like acid; and increasing oxidant parameters while decreasing antioxidant parameters. Classic antiulcer drugs are known to produce antiulcer effects by activating against indomethacin (increasing PGE2, mucus, and bicarbonate production; inhibiting acid secretion; decreasing oxidant parameters; and increasing antioxidants). However, some antiulcer drugs have been shown to inhibit indomethacin-induced ulcers without affecting acid and mucus secretion or oxidant parameters, as well as to inhibit the production of protective factors like COX-1, PGE2, and bicarbonate, and to reduce antioxidant parameters. In order to resolve the contradictions in the abovementioned data, this review hypothesized a relationship between indomethacin-induced ulcers and α 2 adrenergic receptors. It is suggested that blockage of α 2 adrenergic receptors may be responsible for the increase in the aggressive factors induced by indomethacin, and stimulation of α 2 adrenergic receptors may be responsible for the increase of protective factors induced by antiulcer drugs.

Key words

indomethacin ulcer adrenergic receptors 



We would like to express our thanks to Research Assistant Mss. Beyzagul Polat for her contribution to this work.


None of the authors has any conflict of interest to disclose.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Halis Suleyman
    • 1
    Email author
  • Abdulmecit Albayrak
    • 1
  • Mehmet Bilici
    • 2
  • Elif Cadirci
    • 3
  • Zekai Halici
    • 1
  1. 1.Faculty of Medicine, Department of PharmacologyAtaturk UniversityErzurumTurkey
  2. 2.Faculty of Medicine, Department of Internal MedicineAtaturk UniversityErzurumTurkey
  3. 3.Faculty of Pharmacy, Department of PharmacologyAtaturk UniversityErzurumTurkey

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