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.
Abdelmawla
A H
AH
Department of Psychiatry, Queen's Medical Centre, Nottingham, UK.
Langley
R W
RW
Szabadi
E
E
Bradshaw
C M
CM
D000293:Adolescent; D000328:Adult; D000639:Amitriptyline / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010919:Placebos; D012472:Salivation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins / Q000187:drug effects* / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D010919:Placebos; D000639:Amitriptyline; D008729:Methoxamine; D009638:Norepinephrine