AIM OF THE STUDY: Yueju-Wan (YJ), a traditional Chinese medicinal formula, is commonly used for the treatment of depression-related syndromes in China. This study was conducted to evaluate the antidepressant activity of YJ ethanol extract (YJ-E) and its four different fractions, the petroleum ether fraction (YJ-EA), ethyl acetate fraction (YJ-EB), n-butanol fraction (YJ-EC) and final aqueous fraction (YJ-ED). MATERIALS AND METHODS: Two experimental despair animal models: the mice tail suspension test (TST) and the mice forced swimming test (FST) were used to evaluate the antidepressant activity of YJ-E and its fractions. These extracts or fractions were administered orally for 7 days, while the parallel positive control was given at the same time using fluoxetine hydrochloride (FLU) in TST and imipramine hydrochloride (IMI) in FST respectively. RESULTS: YJ-E high dose (YJ-E2), YJ-EA, YJ-EC and the positive control groups could decrease the duration of immobility in the TST and FST and have no significant changes in locomotor activity. YJ-E low dose (YJ-E1), YJ-EB, YJ-ED and the vehicle solvent (VEH) control group have no obvious effect on these same tests. CONCLUSIONS: In these despair animal models, YJ ethanol extract, the petroleum ether fraction and n-butanol fraction show potent antidepressant effects. The petroleum ether fraction and n-butanol fraction appear to be the active fractions of YJ-E. 相似文献
Platelet 3H-imipramine binding was examined in a cross-sectional study of 70 Caucasian women in pregnancy and the early post-partum period, and in 23 nonpregnant women of childbearing age. Mood was also assessed in the pregnancy and post-partum sample. No significant differences in number of binding sites (Bmax) were found, but an increase in the equilibrium dissociation constant (Kd) was demonstrated at 5-7 days post-partum. 相似文献
Abstract The relationship between the genetic polymorphism of S-mephenytoin 4'-hydroxylation catalyzed by CYP2C19 and the N-demethylation of imipramine was examined in 10 Japanese depressed patients. Five patients, who were poor metabolizers of S-mephenytoin, were determined to be either homozygous for a mutation in exon 5 or heterozygous for mutations in exon 4 and exon 5 of the CYP2C19 gene. In contrast, five patients, who were extensive metabolizers, had no mutations. The demethylation index (the desipramine/imipramine ratio) was significantly lower in patients with genetic defects. Plasma levels of imipramine and 2-hydroxyimipramine normalized by the daily dose (mg) per weight (kg) were significantly higher in patients with genetic defects. This suggests that the N-demethylation of imipramine is impaired in patients with genetic defects in the CYP2C19 gene, and that genotype determination may be useful in preventing side effects induced by unexpectedly elevated levels of imipramine. 相似文献
Summary The pharmacokinetic characteristics of imipramine were studied after a single, oral, 100 mg dose was taken by 12 healthy male subjects following 3 days of pretreatment with placebo, cimetidine (300 mg every 6 h), and ranitidine (150 mg every 12 h) in a randomized, double blind, crossover trial. After each imipramine dose plasma samples were collected for 72 h and assayed for imipramine, desipramine, 2-hydroxyimipramine and 2-hydroxydesipramine by HPLC. Cimetidine preadministration statistically prolonged imipramine t1/2 compared to ranitidine (22.7 vs. 13.0 h) or placebo (10.8 h). Mean imipramine area under the curve (AUC) following cimetidine pretreatment was more than double that following placebo (2.633 vs. 0.966 µg·h·ml–1) or ranitidine (1.14 µg·h·ml–1) pretreatment. Imipramine apparent oral clearance was reduced in all 12 subjects after cimetidine. Compared to ranitidine or placebo, cimetidine pretreatment was associated with an increased imipramine/desipramine AUC ratio, suggesting cimetidine-induced impairment of demethylation of imipramine. Ranitidine was not observed to alter imipramine pharmacokinetics. 相似文献
1. 1. Repeated administrations of trazodone as well as imipramine or mianserin(10 mg/kg i.p. twice daily for 3 weeks) attenuated the norepinephrine (NE) stimulation of adenylate cyclase studied in brain minces. Therefore trazodone shares with “tricyclic” (imipramine) and “atypic” (mianserin) antidepressants the capability to modulate the beta-adrenergic function.
2. 2. Daily treatments with imipramine or trazodone enhanced the Vmax of neural uptake of serotonin (5HT) in minces prepared from rat frontal cortex; in contrast mianserin failed to modify the [3H]-5HT uptake.
3. 3. Repeated administrations of imipramine but not of trazodone or mianserin reduced the maximum number of [3H]-imipramine recognition sites which are located on serotonergic axon terminals.
4. 4. Differently, only repeated administration of trazodone decreased Bmax values of [3H]-mianserin binding sites which are located on membranes innervated by serotonergic neurons. Moreover trazodone did not change the number or affinity of 5HT2 receptors either after single or repeated administrations; in contrast even a single administration with mianserin or repeated administrations with imipramine down-regulated [3H]-ketanserin specific binding in membranes prepared from the frontal cortex.
5. 5. Our observations therefore suggest that trazodone, imipramine or mianserin exerts similar effects on the adenylate cyclase system, by acting on a interneuronal loop which links serotonergic and noradrenergic transmission function. However, its exact mechanism of action, in part resembling both tricyclic and atypic antidepressants, requires further exhamination.
The metabolism of imipramine in the brains of rats was analyzed to study the activity of cytochrome P450 in brain microsomes. Brain microsomes were capable of metabolizing imipramine to both hydroxylated and N-demethylated products. The use of selective inhibitors of different cytochromes P450 effected varying changes in the metabolic profiles of formed metabolites consistent with the involvement of several P450 forms in imipramine metabolism. Quinidine inhibited the hydroxylation of imipramine competitively by 60% and 98% at concentrations of 10 μM and 100 μM, respectively. Ketoconazole and 7,8-benzoflavone at a concentration of 100 μM inhibited N-demethylation of imipramine by 75% and 30%, respectively, with a lower effect on imipramine hydroxylation. Results from studies on the incorporation of cytochrome P450 reductase into the brain microsomal system reveal a reductase concentration-dependent increase in imipramine metabolism and suggest that the reductase level in brain is an important factor for the study of catalytic activities in brain microsomal systems. 相似文献
Uptake of radioactive 5-hydroxytryptamine (5-HT) by platelets from rats treated intraperitoneally with the insecticide/acaricide chlordimeform (CDF) at 25 mg/kg was not significantly influenced at 1 h; however, uptake of this amine by platelets from rats treated with its N- monodemethyl metabolite (DMC) at the same dosage was significantly inhibited (37%). Two reversed phase high performance liquid chromatographic systems with electrochemical detection were developed with a capacity to separate 11 biogenic amines and related compounds. Only 5-HT, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were consistently detected in platelets and plasma samples. At 1 h and/or 24 h postinjection, CDF effected significant decreases in platelet levels of 5-HT, NE, and DA and plasma levels of 5-HT, whereas platelet and plasma levels of DOPAC were significantly increased. DMC effected significant decreases in both platelet and plasma levels of 5-HT. These in vivo studies confirmed previous in vitro experiments which demonstrated that formamidines inhibited uptake of 5-HT by platelets and released endogenous stores of amines from platelets. 相似文献
The effect of long-term treatment with the tricyclic antidepressants imipramine (IMI) and desmethylimipramine (DMI) on neuronal responsiveness to 5-hydroxytryptamine (5-HT) was examined in the hippocampal slice preparation from the rat. Population spikes, evoked by electrical stimulation of the stratum radiatum, were recorded in the pyramidal cell layer of the CA1 region of the isolated hippocampus. When 5-HT (10(-7) to 2 X 10(-5) M) was applied there was an initial increase followed by a decrease in the amplitude of the population spike. On washout of 5-HT the amplitude increased transiently above control levels. Daily injection of 10 mg/kg of imipramine or desmethylimipramine, intraperitoneally, into rats for 4-5 weeks was found to produce a significant decrease in the inhibitory effect of 10(-5) M 5-HT, whereas there was no apparent change in the excitatory effects. The acute application of 10(-5) M imipramine or desmethylimipramine antagonized the inhibitory effect of 10(-5) M 5-HT without affecting the excitatory effects. Acute application of the 5-HT receptor antagonists cyproheptadine (10(-5) M) and ketanserin (7.5 X 10(-6) M) completely prevented the appearance of the inhibitory effect of 10(-5) M 5-HT without affecting the excitatory effects. It was concluded that the decreased inhibitory effect of 5-HT which was produced by chronic treatment with imipramine or desmethylimipramine was probably due to a reduction in the number of 5-HT receptors or a reduction in the post-receptor effector mechanisms for 5-HT. 相似文献