THE OPPOSITE EFFECTS OF AMITRIPTYLINE ON NORADRENALINE AND METHOXAMINE EVOKED VENOCONSTRICTION IN MAN

The effects of a single oral dose (100 mg) of amitriptyline on noradre naline- and methoxamine-evoked venoconstriction were compared, using t he dorsal hand vein compliance technique, in 8 healthy male volunteers . Both noradrenaline and methoxamine produced dose-dependent venoconst riction; the geometric mean ED(50) for noradrenaline was 4.15 ng min(- 1) and for methoxamine was 1143.54 ng min(-1); the potency ratio (nora drenaline/methoxamine) was 277. Amitriptyline shifted the dose-respons e curve for noradrenaline to the left (ANOVA: P < 0.025; dose-ratio: 0 .38) consistent with potentiation, and the dose-response curve for met hoxamine to the right (ANOVA: P < 0.025; dose ratio: 2.72) consistent with antagonism. The potentiation is likely to be due to noradrenaline uptake blockade, whereas the antagonism is likely to reflect the bloc kade of post-junctional alpha(1)-adrenoceptors.