Watanabe S, Ohta H, Ohno M, Tani Y, Furuya Y, Ueki S, Man'no K, Sugihara K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Arzneimittelforschung. 1988 Mar;38(3):332-40.
The electroencephalographic (EEG) effect of (-)-trans-4-(4'-fluorophenyl)-3-(3',4'-methylene-dioxyphenoxy-met hyl)piperidine hydrochloride (paroxetine, BRL 29060A) a new antidepressant, was investigated in conscious rabbits with chronic electrode implants and was compared with those of imipramine and amitriptyline. Paroxetine induced an arousal pattern of the spontaneous EEG consisting of low voltage fast waves in the cortex and synchronization of hippocampal theta waves with decreased amplitude, while imipramine and amitriptyline elicited drowsy patterns of the spontaneous EEG. Paroxetine failed to suppress the EEG arousal responses induced not only by auditory stimulation but also by electrical stimulation of the mesencephalic reticular formation, centromedian thalamus and posterior hypothalamus, whereas imipramine and amitriptyline markedly inhibited these responses. The EEG arousal response induced by i.v. injection of physostigmine 0.2 mg/kg was slightly enhanced by paroxetine, while the response was significantly suppressed by imipramine and amitriptyline. Paroxetine, imipramine and amitriptyline showed no significant effect on the photic driving response and recruiting response. Paroxetine did not show any effects on the limbic afterdischarges elicited by either hippocampal or amygdaloid stimulation, while imipramine and amitriptyline caused an initial suppression followed by slight enhancement of these afterdischarges. These results indicate paroxetine to be an antidepressant of a new type which induces a sustained arousal pattern of the spontaneous EEG and has no central anticholinergic action.
研究了新型抗抑郁药盐酸（-）-反式-4-（4'-氟苯基）-3-（3'，4'-亚甲二氧基苯氧基甲基）哌啶（帕罗西汀，BRL 29060A）对慢性植入电极的清醒家兔的脑电图（EEG）效应，并与丙咪嗪和阿米替林进行了比较。帕罗西汀可诱导自发EEG出现觉醒模式，表现为皮质低电压快波以及海马θ波同步化且振幅降低，而丙咪嗪和阿米替林则引发自发EEG的嗜睡模式。帕罗西汀不仅不能抑制由听觉刺激引起的EEG觉醒反应，也不能抑制中脑网状结构、丘脑中央中核和下丘脑后部的电刺激所引起的EEG觉醒反应，而丙咪嗪和阿米替林则能显著抑制这些反应。静脉注射0.2mg/kg毒扁豆碱所诱导的EEG觉醒反应，帕罗西汀使其稍有增强，而丙咪嗪和阿米替林则使其显著抑制。帕罗西汀、丙咪嗪和阿米替林对光驱动反应和募集反应均无显著影响。帕罗西汀对海马或杏仁核刺激所引发的边缘性后放电没有任何影响，而丙咪嗪和阿米替林则先使其抑制，随后稍有增强。这些结果表明，帕罗西汀是一种新型抗抑郁药，可诱导自发EEG出现持续的觉醒模式，且无中枢抗胆碱能作用。
