【摘 要】
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Backbround:Venlafaxine is a new antidepressant that has a chemical structure and neuropharmacologic profile distinct from those of existing antidespressants.The studies about the mechanism of pharmaco
【机 构】
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Clinical Pharmacy&Pharmacology Research Institute,Second Xiangya Hospital,Central South University,C
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Backbround:Venlafaxine is a new antidepressant that has a chemical structure and neuropharmacologic profile distinct from those of existing antidespressants.The studies about the mechanism of pharmacological action of venlafaxine mostly investigated the effects of venlafaxine on 5-HT,NE and DA levels,while only few studies examined the effects on the metabolites levels and ratio of these monoamines neurotransmitters.Aim:To study the biochemical mechanism of venlafaxine through determining the metabolism of monoamine neurotransmitters in brain tissues of rat model of depression after administration ofvenlafaxine using metabonomic method.Materials and methods:The rat model of depression was established by using the methods of separation and chronic unpredictable stress.The determination of 5-hydroxytryptamine (5-HT),norepinephrine (NE),dopamine (DA) and their metabolites,i.e.,5-hydroxyindole-3-acetic acid (5-HIAA),4-hrdroxy-3-methoxyphenylglycol (MHPG) sulfate,3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat brain tissues by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) following chronic administration of different venlafaxine doses (8,16,32mg·kg-1) and saline solution for 14 days.Linear discriminant analysis (LDA) and principal components analysis (PCA) were used in data analysis of metabonomic.Results:Compared with saline,venlafaxine could significantly increase brain 5-HT and NE levels at middle dose (16 mg·kg-1) or high dose (32 mg·kg-1),especially at middle dose.These increases were greater than those seen with the comparable dose of SSRI,fluoxetine,under the same experimental conditions.Conclusion:Venlafaxine lower brain neurotransmitter metabolite levels by decreasing brain neurotransmitters turnover.Venlafaxine could correct the disorder of neurotransmitters metabolism and coordinate the balance of 5-HT,NE and DA to reach the anti-depressed function.
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