The effect of repeated treatment with oxaprotiline enantiomers on central 5-HT receptor subpopulations.
The effect of repeated administration of (+)-OXA (a noradrenaline (NA) uptake inhibitor) and (-)-OXA (devoid of an effect on the NA uptake, but a clinically active antidepressant drug) on central 5-HT receptor subpopulations was studied. (-)-OXA given repeatedly, but not acutely, attenuated the 8-OH-DPAT-induced hypothermia in mice. (+)-OXA administered acutely, as well as repeatedly, was inactive in that test. The 8-OH-DPAT-induced syndrome in rats was attenuated by both OXA isomers administered either acutely or repeatedly. The hypothermia induced by m-CPP in mice was attenuated by single-dose administration of (+)-OXA and (-)-OXA; when given repeatedly, (+)-OXA increased the action of m-CPP. (-)-OXA administered repeatedly was inactive in that test. Either single or repeated administration of (+)-OXA had practically no effect on the depression of exploratory activity induced by m-CPP. (-)-OXA administered acutely or repeatedly attenuated the effect of m-CPP in the same manner. Acute, but not chronic, administration of (-)-OXA reduced the number of head-twitch episodes induced by 5-HTP in mice. Repeated, but not acute, treatment with (+)-OXA attenuated the effect of 5-HTP. The obtained results indicate that (+)-OXA administered repeatedly increases the reactivity of 5-HT1B receptors, decreases the reactivity of 5-HT2 receptors, and has no effect on the reactivity of 5-HT1A- (pre- and postsynaptic) and 5-HT1C-receptors. (-)-OXA given repeatedly decreases the reactivity of presynaptic 5-HT1A receptors and has no influence on the reactivity of postsynaptic 5-HT1A-, 5-HT1B-, 5-HT1C- and 5-HT2-receptors.
Dereń-Wesołek
A
A
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Maj
J
J
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000032:analysis / Q000187:drug effects*; D013237:Stereoisomerism
D000928:Antidepressive Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D008376:Maprotiline; C027299:hydroxymaprotilin; C011799:5-hydroxy-2-N,N-dipropylaminotetralin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015068:1-(3-chlorophenyl)piperazine