The mode of action of tetrabenazine on peripheral noradrenergic nerves.

1. Tetrabenazine (100 mg/kg i.p. in rats) greatly decreased catecholamine-induced histofluorescence in the iris, hepatic portal vein, inferior vena cava and mesenteric blood vessels 4 h after injection. Fluorescence returned to normal by 24 h after injection. 2. The extent of this depletion (4 h after tetrabenazine) was similar to that seen 18 h after reserpine (0.5 mg/kg i.p.). 3. Incubation of tissues taken from rats 4 h after this dose of tetrabenazine with noradrenaline 5 X 10(-6)M restored the intraneuronal fluorescence as well as the electron density of noradrenergic vesicle cores viewed with the electron microscope. No such repletion was seen on incubation of tissues from reserpine-treated rats with noradrenaline under the same conditions. 4. Incubation of tetrabenazine-treated hepatic portal veins with noradrenaline also reinstated the normal response to electrical stimulation of the intramural nerves. This did not occur with reserpine-treated veins. 5. The interpretation that tetrabenazine exerts a reversible depleting effect on the noradrenergic vesicle is supported by the demonstration that it exerts no monoamine oxidase inhibiton.