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 noradrenaline- and methoxamine-evoked venoconstriction were compared, using the dorsal hand vein compliance technique, in 8 healthy male volunteers. Both noradrenaline and methoxamine produced dose-dependent venoconstriction; the geometric mean ED50 for noradrenaline was 4.15 ng min-1 and for methoxamine was 1143.54 ng min-1; the potency ratio (noradrenaline/methoxamine) was 277. Amitriptyline shifted the dose-response curve for noradrenaline to the left (ANOVA: P < 0.025; dose-ratio: 0.38) consistent with potentiation, and the dose-response curve for methoxamine 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 blockade of post-junctional alpha 1-adrenoceptors.