Oxaprotiline: enantioselective noradrenaline uptake inhibition indicated by intravenous amine pressor tests but not alpha 2-adrenoceptor binding to intact platelets in man

The optically active isomers of the racemic tetracyclic antidepressant oxaprotiline, R (-) oxaprotiline CGP 12,103 A (levoprotiline) and the S (+) oxaprotiline CGP 12,104 A, have been used as tools for a methodological Phase I study. Only the S (+) enantiomer CGP 12,104 A inhibits noradrenaline uptake. Intravenous amine pressor tests and ex vivo measurement of alpha 2-adrenoceptor binding to intact human platelets were compared with respect to their reliability in indicating CGP 12,104 A-induced amine uptake inhibition and possibly associated alpha 2-receptor down-regulation in healthy subjects. alpha 2-Adrenoceptor binding on intact human platelets did not distinguish between CGP 12,104 and CGP 12,103 A. However, amine pressor tests reflected the amine uptake inhibiting effect of CGP 12,104 A as a 5-fold decrease in tyramine pressor sensitivity and a 5-fold increase in noradrenaline pressor sensitivity.