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 α2-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 α2-receptor down-regulation in healthy subjects.
α2-Adrenoceptor binding on intact human platelets did not distinguish between CGP 12 104 A 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 sensivity and a 5-fold increase in noradrenaline pressor sensitivity.
Oxaprotiline Levoprotiline noradrenaline uptake inhibitors enantiomers CGP 12 103 A CGP 12 104 A amine pressor tests α2-adrenoceptor binding intact human platelets