The noradrenaline uptake inhibitor, (+)-oxaprotiline, but not the inactive enantiomer, (-)-oxaprotiline, inhibits sympathetic nerve activity in the rabbit: involvement of adrenoceptors.

The effect of the enantiomers of oxaprotiline on the sympathetic nervous system was studied in anesthetized rabbits. (+)-Oxaprotile 0.2, 0.6 and 1.8 mg kg-1 dose dependently reduced prostganglionic renal sympathetic nerve activity and the clearance of [3H]noradrenaline from the plasma but increased the plasma noradrenaline concentration. The spillover of noradrenaline into the blood was not changed significantly, nor were blood pressure and heart rate, except transiently. The same doses of (-)-oxaprotiline had no effect on any of the parameters measured. (+)-Oxoprotiline also reduced lumbar preganglionic sympathetic nerve activity. The effect of (+)-oxaprotiline on renal sympathetic nerve activity was only minimally antagonized by yohimbine given alone. (+)-Oxaprotiline also inhibited renal sympathetic nerve activity after treatment with prazosin and propranolol. Subsequent administration of yohimbine restored sympathetic nerve activity to the value seen before the administration of (+)-oxaprotiline. The results show that inhibition of the re-uptake of released noradrenaline is the basis of the sympathoinhibition produced by (+)-oxaprotiline. Noradrenaline probably acts on alpha 2-adrenoceptors in the central nervous system to produce sympathoinhibition.