کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2537128 | 1559180 | 2006 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The involvement of a cyclooxygenase 1 gene-derived protein in the antinociceptive action of paracetamol in mice The involvement of a cyclooxygenase 1 gene-derived protein in the antinociceptive action of paracetamol in mice](/preview/png/2537128.png)
Paracetamol is a widely used analgesic and antipyretic with weak anti-inflammatory properties. Experimental evidence suggests that inhibition of prostaglandin biosynthesis contributes to its pharmacological actions. Three cyclooxygenase (COX) isoenzymes are involved in prostaglandin biosynthesis, COX-1, COX-2 and a recently discovered splice-variant of COX-1, COX-3. Our aim was to identify the relative roles for these enzymes in the antinociceptive action of paracetamol in mice. We compared the antinociceptive action of paracetamol with the non-selective non-steroid anti-inflammatory drug, diclofenac and studied paracetamol antinociception in COX-1 and COX-2 knockout mice.Paracetamol (100–400 mg/kg) inhibited both acetic acid- and iloprost-induced writhing responses. In contrast, diclofenac (10–100 mg/kg) inhibited only acetic acid-induced writhing. Only diclofenac reduced peripheral prostaglandin biosynthesis whereas both drugs reduced central prostaglandin production. Prostaglandin E2 (PGE2) concentrations were reduced in different brain regions by administration of paracetamol. COX-1, COX-2 and COX-3 enzyme proteins were expressed in the same brain regions. The effects of paracetamol on writhing responses and on brain PGE2 levels were reduced in COX-1, but not COX-2, knockout mice. The selective COX-3 inhibitors, aminopyrine and antipyrine also reduced writhing responses and brain PGE2 biosynthesis. These results suggest that the antinociceptive action of paracetamol may be mediated by inhibition of COX-3.
Journal: European Journal of Pharmacology - Volume 538, Issues 1–3, 24 May 2006, Pages 57–65