On the use of selective neurotoxic amine analogs to measure the blockade of norepinephrine and 5-hydroxytryptamine uptake systems by antidepressants.

In pargyline or carbidopa pretreated mice, 6-hydroxydopa causes a depletion of brain norepinephrine. Several antidepressant compounds block the depletion after pargyline but not after carbidopa pretreatment. Similarly, p-chloromethamphetamine-induced depletion of brain 5-hydroxytryptamine is blocked by several antidepressants. Diazepam antagonizes the ability to imipramine to block the norepinephrine depletion induced by 6-hydroxydopa but not the 5-hydroxytryptamine depletion induced by p-chloromethamphetamine. Blockade of selective neurotoxic induced depletions of biogenic amines is a useful in vivo technique for determining the effects of drugs on the amine uptake systems. However, the results for compounds with mixed antidepressant/anxiolytic activity must be viewed with caution.