[Non-steroidal anti-inflammatory drugs and cyclooxygenase-2 selectivity in gastroenterology].
The discovery of, at least, two isoforms of the enzyme cyclooxygenase, named by the numbers 1 and 2, has updated our knowledge about the NSAID. This has led investigators to reconsider what we can expect from this kind of drugs. The two isoforms share enzymatic and structural properties, although they are regulated differently, at molecular level and can be distinguished from their functions, although an overlap of roles between them do exist. The main goal of the development of highly selective inhibitors is to improve gastric tolerability. The classical NSAID inhibit preferentially the isoform 1 of the cyclooxygenase, in vitro, which appears to be dangerous, according to gastrointestinal safety profile. The new compounds with high selectivity for the isoform 2 of the cyclooxygenase could be better tolerated at gastrointestinal level. Meanwhile these compounds also could have a potential use in several diseases such as colorectal cancer and neurodegenerative processes. The potential occurrence of side effects, perhaps related with renal function, should be noted. Finally large controlled clinical trials are needed to estimate the therapeutic advantages which can be offered by the new highly selective NSAID, and the potential consequences which can result from the isoform 2 of the cyclooxygenase prolonged inhibition
Ledro Cano
D
D
Servicio de Aparato Digestivo, Area Hospitalaria "Virgen Macarena", Sevilla, España.
Gómez Rodríguez
B J
BJ
Torres Domínguez
Y
Y
Hergueta Delgado
P
P
Herrerías Esteban
J M
JM
Herrerías Gutiérrez
J M
JM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases