Pharmacological studies with several analogs of mazindol: correlation between effects on dopamine uptake and various...

Several structural analogs of mazindol were tested as inhibitors of the uptake of [3H] dopamine in rat neostriatum, of [3H] norepinephrine in rat occipital cortex and of [3H] serotonin in whole rat brain. A rather wide range of potencies was observed but a number of the drugs were even more potent than mazindol as uptake inhibitors. All of the drugs studied were weak releasing agents for previously accumulated [3H]amines. Several of the drugs caused large increases in motor activity in normal mice but not in reserpinized mice. However, these same drugs were able to prevent amphetamine-induced increases in activity in reserpinized mice, and were able to induce ipsilateral circling in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. Two of these same drugs were tested and found to be potent inhibitors of prolactin secretion. Correlations will be made between the capacities of the drugs to inhibit dopamine uptake and the in vivo responses mentioned above.