In vitro and in vivo vasodilator activity of racemic tramadol and its enantiomers in Wistar rats.
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.
Raimundo
Juliana Montani
JM
Departamento de Farmacologia Basica e Clinica, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude, Instituto de Ciencias Biomedicas, Brazil.
Sudo
Roberto Takashi
RT
Pontes
Luana Braga
LB
Antunes
Fernanda
F
Trachez
Margarete Manhães
MM
Zapata-Sudo
Gisele
G
D000109:Acetylcholine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D014147:Tramadol / Q000737:chemistry / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000701:Analgesics, Opioid; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D009270:Naloxone; D014147:Tramadol; D000109:Acetylcholine