In vitro and in vivo vasodilator activity of racemic tramadol and its enantiomers in Wistar rats

• Published in: European journal of pharmacology 2006-01, Vol.530 (1), p.117-123
• Main Authors: Raimundo, Juliana Montani, Sudo, Roberto Takashi, Pontes, Luana Braga, Antunes, Fernanda, Trachez, Margarete Manhães, Zapata-Sudo, Gisele
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Analgesics, Opioid - pharmacology; Animals; Aorta; Aorta, Thoracic - drug effects; Aorta, Thoracic - physiology; Biological and medical sciences; Blood Pressure - drug effects; Dose-Response Relationship, Drug; Electric Stimulation; Electrocardiography; Enantiomers; Endothelium, Vascular - physiology; Heart Rate - drug effects; In Vitro Techniques; Isometric Contraction - drug effects; Male; Medical sciences; Naloxone; Naloxone - pharmacology; Papillary muscle; Papillary Muscles - drug effects; Papillary Muscles - physiology; Pharmacology. Drug treatments; Phenylephrine - pharmacology; Rats; Rats, Wistar; Stereoisomerism; Tramadol; Tramadol - chemistry; Tramadol - pharmacology; Vasoconstrictor Agents - pharmacology; Vasodilatation; Vasodilation - drug effects; Vasodilator Agents - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.11.028

Tramadol ((±)-tramadol) is an analgesic agent formulated as a racemic mixture (1 : 1) of (−)- and (+)-tramadol, which differ in their potency to bind to μ-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 μ-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.