The effect of (+)- and (-)-oxaprotiline administered repeatedly on the dopamine system.
The behavioural and biochemical effects of repeated (14 and 28 days) treatment with (+)-oxaprotiline (a noradrenaline uptake inhibitor) and (-)-oxaprotiline (levoprotiline, without influence on noradrenaline uptake; the clinically active antidepressant) were studied in rats. Both those enantiomers given repeatedly increased the locomotor and exploratory activity and reduced the immobility time in Porsolt's test. The D-amphetamine-induced locomotor hyperactivity, as well as the stereotypies induced by D-amphetamine and apomorphine, were increased by the oxaprotilines. Single-dose treatment with both the oxaprotilines was not effective in the tests mentioned above. Repeated (+)-oxaprotiline administration reduced the binding (Bmax but not KD) to dopamine D-1 receptors in the striatum and limbic system; levoprotiline was inactive. The binding to dopamine D-2 receptors was not changed by either drug. Both the enantiomers showed only low affinity for brain dopamine D-1 and D-2 receptors in vitro. The obtained results indicate that chronic treatment with (+)- and (-)-oxaprotiline increases behavioural responsiveness of the dopamine mesolimbic and striatal systems.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Klimek
V
V
Rogóz
Z
Z
Skuza
G
G
Sowińska
H
H
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects; D013550:Swimming
D000928:Antidepressive Agents; D001552:Benzazepines; D011954:Receptors, Dopamine; D008376:Maprotiline; C027299:hydroxymaprotilin; D013134:Spiperone; D001058:Apomorphine; D003913:Dextroamphetamine