Early effects of monoamine oxidase inhibitors on dopamine metabolism and monoamine oxidase activity in the neostriatum of the rat

Summary Dopamine levels in the neostriatum of the rat were estimated at various times after pargyline (75 mg/kg), pheniprazine (4 mg/kg) and tranylcypromine (20 mg/kg) intraperitoneal injections. Depending on the inhibitor used, the amine levels reached 135 to 150% of control values within 10 min. During the 20 min which followed this rapid linear rise, DA levels increased in tissues at a much slower rate. As indicated by the estimation of MAO activity using¹⁴C-tyramine or kynuramine as substrates, the three drugs induced a complete inhibition of the enzyme activity within 5 min. A similar effect was seen after pheniprazine and tranylcypromine with¹⁴C-dopamine as substrate, but the maximal inhibition never exceeded 80% after pargyline treatment. As revealed by the in vivo 3 min initial accumulation of³H-H²O seen at the end of a local infusion of L. 3. 5-³H-tyrosine, the rate of the first step of DA synthesis was unchanged 5 min after pargyline treatment but significantly reduced 10 min after the drug injection. This explains the sudden interruption in the rise of DA levels observed shortly after the MAO inhibitors injection. DA synthesis rate was calculated from the initial (5 min) rate of DA accumulation and was found to be 148 to 190 nmole/g/hr depending on the inhibitor used.