Smith J E, Lakoski J M
Department of Pharmacology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Eur J Pharmacol. 1997 Mar 26;323(1):69-73. doi: 10.1016/s0014-2999(97)00024-1.
The cellular electrophysiological effects of duloxetine (LY248686), a dual serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine reuptake inhibitor, and the selective serotonin reuptake inhibitor fluoxetine were compared on spontaneously active neurons in the dorsal raphe nucleus and the hippocampus of chloral hydrate-anesthetized male rat. Systemic intravenous administration of duloxetine or fluoxetine inhibited dorsal raphe nucleus cell firing in a dose-dependent manner; duloxetine suppressed cell firing at significantly lower doses (ED100 1.4 +/- 0.3 mg/kg) than fluoxetine (ED100 10.0 +/- 2.0 mg/kg). In the hippocampus, microiontophoretic application of duloxetine or fluoxetine (0.01 M, pH 5.5; 5-40 nA) produced minimal inhibition of cell firing. When duloxetine was co-applied with 5-HT, the recovery response (RT50 values) of hippocampal pyramidal neurons to 5-HT application was not altered. In contrast, co-application of fluoxetine with 5-HT at the same iontophoretic currents significantly increased (59%) the RT50 values produced by 5-HT application alone. This physiological and pharmacological study contributes to understanding the cellular mechanisms of these agents which may be useful in the treatment of depression.
在水合氯醛麻醉的雄性大鼠的中缝背核和海马中，比较了5-羟色胺（5-HT）和去甲肾上腺素再摄取双重抑制剂度洛西汀（LY248686）与5-羟色胺再摄取抑制剂氟西汀对自发活动神经元的细胞电生理效应。静脉全身给药度洛西汀或氟西汀以剂量依赖性方式抑制中缝背核细胞放电；度洛西汀在比氟西汀（ED100 10.0±2.0mg/kg）低得多的剂量（ED100 1.4±0.3mg/kg）时就能抑制细胞放电。在海马中，微量离子电泳施加度洛西汀或氟西汀（0.01M，pH5.5；5-40nA）对细胞放电产生的抑制作用极小。当度洛西汀与5-羟色胺共同施加时，海马锥体细胞对5-羟色胺施加的恢复反应（RT50值）未改变。相反，在相同离子电泳电流下，氟西汀与5-羟色胺共同施加时，单独由5-羟色胺施加产生的RT50值显著增加（59%）。这项生理和药理学研究有助于理解这些药物的细胞机制，这可能对治疗抑郁症有用。
