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.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002230:Carbidopa / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*
D000928:Antidepressive Agents; D012701:Serotonin; D008694:Methamphetamine; D004295:Dihydroxyphenylalanine; D010293:Pargyline; D002230:Carbidopa; D007099:Imipramine; D003975:Diazepam; D009638:Norepinephrine