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.
Human Pharmacology Institute Ciba-Geigy, Tübingen, FRG.
I W
IW
Reimann
L
L
Firkusny
K H
KH
Antonin
P R
PR
Bieck
D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D003864:Depression, Chemical; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011485:Protein Binding; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D016037:Single-Blind Method; D013237:Stereoisomerism; D014439:Tyramine
D000928:Antidepressive Agents; D011942:Receptors, Adrenergic, alpha; D008376:Maprotiline; C027299:hydroxymaprotilin; D009638:Norepinephrine; D014439:Tyramine