The selectivity of the naturally occurring amine, N,N-dimethyltyramine (hordenine) for monoamine oxidase (MAO) and its action upon isolated vasa deferentia of the rat was investigated. Hordenine was deaminated by rat liver MAO with a Michaelis constant of 479 microM and maximum velocity of 128 nmol (mg protein)-1 h-1 compared with 144 microM and 482 nmol (mg protein)-1 h-1 for tyramine. Studies, with selective irreversible inhibitors of MAO, showed that hordenine was a highly selective substrate for MAO-B of liver and that it was not deaminated by the MAO-A of intestinal epithelium. In contrast to tyramine, hordenine did not produce contractions of isolated vasa deferentia. However, 25 microM hordenine potentiated contractile responses of vasa, from control animals, to submaximal doses of noradrenaline and inhibited responses to tyramine. It did not alter responses, to noradrenaline, of vasa denervated by chronic pretreatment of rats with guanethidine. Therefore, it appears that hordenine acted as an inhibitor of noradrenaline uptake, in isolated vasa deferentia. These results indicate that dietary-hordenine is unlikely to be deaminated by intestinal MAO as this is predominantly MAO-A. Consequently, it is likely to be absorbed and could affect the sympathetic nervous system, by virtue of its action as an inhibitor of noradrenaline uptake.

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Background:Tramadol was recently suggested to be an effective and relatively safe pharmacological treatment for pain and hyperalgesia in urinary colic from calculosis. It can apparently represent a valid therapeutic approach to this medical problem, especially in cases where conventional therapy cannot be applied. However, up to our knowledge, the in vitro effect of tramadol on ureteral smooth muscle contractility has not been investigated. Objectives: The aim of this study is to investigate the effect of tramadol on the ovine spontaneous ureteral activity and attempt to determine its pharmacological basis. Methods: In vitro experiments were performed on ureteral ring preparations in an organ bath. Contractions per minute (frequency) were calculated. The effect of tramadol, was obtained on its own and in the presence of naloxone, chlorpheniramine, phenoxybenzamine, atropine, or diclofenac; while, the effects of histamine, phenylephrine and acetylcholine (ACh) were recorded on their own and in the presence of their respective antagonists. Results: Tramadol (50M) significantly enhanced the spontaneous rhythmic motility (1.21 ± 0.25 to 3.3 ± 0.54). Further, naloxone (2M), chlorpheniramine (M), atropine (M), or diclofenac (10M) failed to inhibit the excitatory effect of tramadol. However, phenoxybenzamine (1M) appreciably attenuated the excitatory effect of tramadol. Conclusions: Tramadol produces substantial excitatory-ureteral activity by a mechanism that is still to be clarified and apparently not dependent on activation of opioid receptors, H1receptors, muscarinic-receptors, or prostanoid synthesis and partly dependent on aminergic mechanisms.