Single treatments with the antidepressant oxaprotiline and its (+) and (-) enantiomers increase behavioural responses to dopaminergic stimulation in the rat.

The effects of single doses of oxaprotiline and its (+)- and (-)-enantiomers (CGP 12 104 A and CGP 12 103 A, provisional generic name levoprotiline) on apomorphine- and amphetamine-induced stereotypies and amphetamine-induced hyperthermia were investigated in the rat. All 3 compounds enhanced and prolonged stereotyped responses to apomorphine and amphetamine at single doses of 10-30 mg/kg i.p. The most active appeared to be the (-)-enantiomer levoprotiline which is devoid of NA-uptake-inhibiting properties. Neither compound, however, potentiated amphetamine-induced hyperthermia, suggesting that enhanced behavioural effects are not due to the interference with metabolic degradation of amphetamine. The mechanism of the observed effect remains obscure, but in view of the reported clinical antidepressant action of levoprotiline these findings are interesting.