Pharmacological characterization of metamizol-induced relaxation in phenylephrine-precontracted rabbit thoracic aorta smooth muscle.
Metamizol produced a dose- and time-dependent relaxation in rabbit thoracic aorta smooth muscle that was precontracted by phenylephrine. Such a relaxation was not observed with indomethacin, which is also a nonsteroidal anti-inflammatory drug. The relaxing effect of metamizol was independent of the presence of vascular endothelium. Tetraethylammonium (a calcium-activated potassium channel inhibitor), glybenclamide (an ATP-dependent potassium channel inhibitor), indomethacin (a cyclooxygenase inhibitor), and methylene blue (a soluble guanylate cyclase inhibitor) did not have any effect on metamizol-induced relaxation response. Metamizol did not produce any relaxation effect on aortic smooth muscle when KCl (30, 60, and 117 mM KCl) was used instead of phenylephrine to precontract the preparation. Ouabain (a Na-K ATPase pump inhibitor) showed a dose-dependent inhibition on metamizol's relaxation response. However, in potassium-free medium, which is an alternative way to block the Na-K ATPase pump, no inhibition in metamizol-induced relaxation response was observed. When metamizol was incubated for 2 h in organ-bath conditions before evaluating its relaxing effect, it produced a relatively faster relaxation, indicating that the relaxing effect of metamizol is produced by one of its (active) spontaneous degradation products (possibly 4-methylaminoantipyrine).
Ergün
H
H
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Ankara University, Sihhiye, Turkey.
Ayhan
I H
IH
Tulunay
F C
FC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004177:Dipyrone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D010042:Ouabain; D004177:Dipyrone; D019789:Tetraethylammonium; D000254:Sodium-Potassium-Exchanging ATPase; D005905:Glyburide; D008751:Methylene Blue; D007213:Indomethacin