Effect of imipramine on 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in rat striatum.
We examined the effect of imipramine (a tricyclic antidepressant drug) on hydroxyl radical (.OH) generation induced by 1-methyl-4-phenylpyridinium ion (MPP(+)) in extracellular fluid of rat striatum, using a microdialysis technique. Imipramine enhanced the formation of.OH trapped as 2,3-dihydroxybenzoic acid (DHBA) induced by MPP(+) (5 mM). Introduction of imipramine (0.1, 0.5 and 1.0 mM) dose-dependently increased the level of dopamine (DA) release. Concomitantly, imipramine enhanced DA efflux and the level of DHBA induced by MPP(+), as compared with MPP(+)-treated control. When corresponding experiments were performed with reserpinized rats, there were small increases in the levels of DA and nonsignificant increase in the formation of DHBA. When iron (II) was administered to imipramine (1 mM)-treated animals, a marked elevation of DHBA was observed, compared with MPP(+)-only treated animals. A positive linear correlation was observed between iron (II) and DHBA (R(2)=0.985) in the dialysate. These results indicate that imipramine enhances generation of.OH induced by MPP(+) during enhanced DA overflow.
Obata
Toshio
T
Department of Pharmacology and Therapeutics, Oita Medical University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan. tobata@oita-med.ac.jp
Egashira
Toru
T
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D005260:Female; D062385:Hydroxybenzoates / Q000032:analysis; D017665:Hydroxyl Radical / Q000032:analysis / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology*; D007769:Lactams / Q000633:toxicity*; D017551:Microdialysis; D008995:Monoamine Oxidase / Q000378:metabolism; D011728:Pyridones / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
C116575:1-methyl-4-phenyl-5,6-dihydro-2-pyridone; D000929:Antidepressive Agents, Tricyclic; D062385:Hydroxybenzoates; D007769:Lactams; D011728:Pyridones; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D008995:Monoamine Oxidase; D007099:Imipramine; D004298:Dopamine