Pharmacological effects of tramadol hydrochloride on blood pressure and on some isolated smooth muscles of experimental animals

ABSTRACT

Tramadol is a centrally acting synthetic opioid analgesic drug. It is an effective analgesic with a good tolerable profile in short term uses. The apparent lack of tolerance and dependence and the low incidence of respiratory depression associated with tramadol suggests that the drug may offer advantages over some of the other established analgesic drugs currently used for relief of moderate to severe pain. This work was carried to investigate tramadol effect on some isolated and intact animal preparations. In in-vivo experiments Intravenous injection of tramadol in anaesthetized cats at doses 0.6 and 1.2 mg/kg caused a significant rise of mean arterial blood pressure which was revealed to be through an alpha1 adrenoceptor agonistic action. However, higher doses of tramadol, [2.4 to 19.2 mg/kg] produced a biphasic change in mean arterial blood pressure; a significant initial decrease followed by a significant increase. The initial decrease in blood pressure was proved to be mediated through a peripheral site of action. Presynaptic alpha2 adrenoceptors were also involved in the decrease of blood pressure. The second phase [increase in blood pressure] was abolished in spinal cat preparation denoting a central site of action. Tramadol [2.4-19.2 mg/kg] also produced a dose dependent and significant decrease in heart rate. Using the cat nictitating membrane preparation showed that tramadol may act partially through inhibition of norepinephrine [NE] reuptake. The drug also significantly potentiated the NE induced contractions of isolated rabbit aortic spiral strip. This potentiation may be attributed to inhibition of NE reuptake. On isolated guinea pig tracheal spiral strip and ileal preparations, tramadol caused a dose depended reduction of the histamine induced contractions. However, the drug caused a significant increase in the height of the contractions of isolated rabbit jejunum. This stimulant action, was proved to involve both serotonergic and opioid receptors. It can be concluded that inspite of tramadol being one of synthetic opioid drugs, it did not show a histamine potentiating effect on the isolated guinea pig tracheal spiral strip. On the other hand it reduced the histamine induced contractions of the preparation which may be of value in patients with tendency to bronchoconstriction. The experiments carried on anaesthetized cats revealed that tramadol produced an elevation of blood pressure accompanied by bradycardia which must be considered especially in patients with cardiovascular disorders