In vitro and in vivo vasodilator activity of racemic tramadol and its enantiomers in Wistar rats |
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Authors: | Raimundo Juliana Montani Sudo Roberto Takashi Pontes Luana Braga Antunes Fernanda Trachez Margarete Manhães Zapata-Sudo Gisele |
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Institution: | Departamento de Farmacologia Basica e Clinica, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude, Instituto de Ciencias Biomedicas, Brazil. |
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Abstract: | Tramadol ((+/-)-tramadol) is an analgesic agent formulated as a racemic mixture (1:1) of (-)- and (+)-tramadol, which differ in their potency to bind to mu-opioid receptors and to inhibit monoamine-reuptake. We investigated the stereoselectivity of in vitro tramadol-induced vasodilatation of aortic rings and its effect on the arterial blood pressure measured in conscious Wistar rats. (+)-Tramadol, but not (-)-tramadol, produced a concentration-dependent relaxation of aorta precontracted with phenylephrine. The concentration-response curve was significantly altered by the removal of endothelium. Vascular relaxation was also inhibited by pre-incubation of endothelium-intact aorta with naloxone, suggesting the involvement of opioid receptors. The vasodilatation produced by tramadol was stereoselective, and the (+)-tramadol-induced vasodilatation was mediated by mu-opioid receptors and partially dependent on endothelium integrity. The hypotensive response induced by (+)-tramadol was also observed after bolus injection of 5.0 and 10.0 mg/kg. The results indicate that only high doses of tramadol cause cardiac depression and hypotension, indicating that it can be used safely. |
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