The human pharmacology of reboxetine

Reboxetine is a novel antidepressant with a potent noradrenaline uptake‐inhibiting property, but with little affinity for neurotransmitter receptors. Desipramine is a classical tricyclic antidepressant which, apart from inhibiting noradrenaline uptake, also has affinity for muscarinic cholinoceptors and α 1 ‐adrenoceptors, which can result in unwanted side effects. Single doses of reboxetine (1, 2 and 4 mg) and desipramine (25, 50 and 100 mg), were compared with placebo in 37 healthy volunteers, on several autonomic functions. Reboxetine antagonised tyramine‐evoked mydriasis, indicating noradrenaline‐uptake blockade in the iris. The antidepressant increased blood pressure, heart rate, and resting pupil diameter and shortened the recovery time of the light reflex response consistent with a sympathomimetic effect resulting from noradrenaline‐uptake blockade in peripheral tissues. Both antidepressants reduced salivation and light reflex amplitude, but failed to antagonise pilocarpine‐evoked miosis, a response mediated by muscarinic cholinoceptors. Therefore, the effects on salivation and light reflex amplitude are unlikely to be due to muscarinic receptor blockade, but may rather reflect enhancement of noradrenergic inhibition of central parasympathetic nuclei as a result of noradrenaline‐uptake blockade. Both antidepressants failed to antagonise phenylephrine‐evoked sweating and methoxamine‐evoked mydriasis, responses mediated by α 1 ‐adrenoceptors, consistent with their low affinity for these receptors. © 1998 John Wiley & Sons, Ltd.