Rapid changes in functional responsiveness of the 5-HT system after single-dose and multiple-dose treatment with antidepressants: effects of maprotiline and oxaprotiline and its enantiomers

Abstract

Functional responsiveness to 5-HTP (L-5-hydroxytryptophan) and quipazine 24 h after one single dose and 24 h and 72 h after repeated administration (2.5 and 10 mg/kg twice daily for 7 days) of maprotiline, oxaprotiline and its (+) and (-) enantiomers was tested in the rat. All compounds markedly increased the behavioural effects of 5-HTP 24 h after one single injection. This effect was further enhanced after repeated treatment. The response to quipazine was less consistently affected than the response to 5-HTP. Neither drug increased the response to quipazine 24 h after the last injection. However, maprotiline and oxaprotiline enhanced the quipazine-induced head-twitch 72 h after the withdrawal of subchronic treat ment, enantiomers failed to do so. This differential effect of drugs in respect to the interactions with 5-HTP and quipazine is, however, not understood at present. The results of this study indicate that only one single dose of antidepressants may change the functional respon siveness of the 5-HT system and that such changes occur rapidly. The results also provide a possible rationale for the suggested antidepressant activity of levoprotiline, the (-) enantiomer of oxaprotiline and otherwise biochemically inactive compound.