吗氯贝胺治疗抑郁症

目的 :比较吗氯贝胺和丙米嗪治疗抑郁症的疗效及不良反应。方法 :10 7例抑郁症分成 3组。吗氯贝胺双盲组 (吗氯贝胺组 ) 2 5例 (男性 16例 ,女性 9例 ;年龄 36a±s 10a) ,予吗氯贝胺 2 0 0mg ,po ,bid。丙米嗪双盲组 (丙米嗪组 ) 2 6例 (男性 14例 ,女性 12例 ;年龄 36a± 12a) ,予丙米嗪 10 0mg ,po ,bid。吗氯贝胺开放组 (开放组 ) 56例 (男性 2 7例 ,女性 2 9例 ;年龄 39a± 13a)予吗氯贝胺 2 0 0mg ,po ,bid ;均 4wk为一个疗程。结果 :吗氯贝胺组有效率 96% ,丙米嗪组 96% ,Ridit分析P >0 .0 5,开放组 95%。药物不良反应发生率丙米嗪组高于吗氯贝胺组。结论 :吗氯贝胺与丙米嗪治疗抑郁症疗效相同 ,不良反应少     

米帕明对谷氨酸损伤中枢神经细胞的保护作用

目的研究米帕明(Imi)对谷氨酸损伤培养大鼠皮层神经细胞的保护作用.方法分离培养15～18 d胎龄的大鼠神经细胞,加入谷氨酸(Glu),观察谷氨酸对神经细胞的损伤作用及米帕明的保护作用.结果加入谷氨酸后,神经细胞出现明显损伤性变化,死亡率升高,培养上清液中乳酸脱氢酶(LDH)、一氧化氮(NO)含量增加,细胞匀浆中丙二醛(MDA)生成增加,超氧化物歧化酶(SOD)含量明显减少.Imi能不同程度地减轻上述损伤性变化.结论 Imi对谷氨酸所致的神经细胞损伤具有保护作用,其作用机制可能与钙拮抗作用有关.     

Qualitative changes in saliva composition after short-term administratio of imipramine and zimelidine in healthy volunteers

Abstract – Ten healthy volunteers participated in a double-blind, controlled, randomized, cross-over trial, where the effects of te antidepressan: drugs imipramine (75 mg/day) and zimelidine (100 mg/day and 200 mg/day) on saliva secretion rate and saliva composition were tested. The saliva secretion decreased and qualitative changes were found. Imipramine (75 mg/day) and zimelidine (200 mg/day), but not zimelidine (100 mg/day), increased buffer capacity and the components of the salivary glycoproteins (sialic, fucose, hexoses). Total proteins, amylase, secretory component and electrolytes (Na⁺, K⁺, Ca⁺⁺, PO₄^3-) did not change significantly.     

Different pharmacokinetic and pharmacological effects following acute and chronic treatment with imipramine

Summary Two schedules of imipramine (IMI) administration were compared, a single intraperitoneal dose (10 mg/kg) (I) and chronic oral dosage (10 mg/kg twice a day for 14 days) (II). During schedule I, IMI reached maximal concentration in brain twice as high as that of its metabolite, desipramine (DMI), but disappeared more rapidly. During schedule II, DMI achieved concentrations twice as high as those of IMI which were maintained in a long-lasting plateau and there were considerable differences in areas of brain concentration curves. During schedule I, depletion of brain noradrenaline (NA) induced by H 77/77 and of 5-hydroxytryptamine (5-HT) by p-chloroamphetamine, were inhibited. During schedule II, after DMI concentration had become high and that of IMI low, only NA depletion but not that of 5-HT, was inhibited. At the same time, fenfluramine-induced hyperthermia was not antagonized although it was inhibited in schedule I. These findings may be relevant to those obtained clinically and may help to shed light on mechanisms of antidepressant action.     

Lofepramine and imipramine in unipolar depressed outpatients

This is a double-blind study involving 158 outpatients diagnosed ac-cording to the DSM-III as suffering from major depressive disorder. Both active drugs produced significantly more improvement than placebo on both physician and patient ratings, and lofepramine produced slightly less sedation and anticholinergic effects when compared with imipramine.     

Comparison of the minimal lethal doses,cardiac toxicities,and cardiodepressor effects of tricyclic antidepressants and UP 614-04, a potential antidepressant

The cardiotoxic and hemodynamic effects of intravenously administered UP 614-04, imipramine, clomipramine, and amitriptyline were compared using guinea pigs and dogs. In guinea pigs, determinations of minimal lethal dose and electrocardioraphic changes indicated that UP 614-04 was much less cardiotoxic than the three tricyclic antidepressants tested. In dogs, both imipramine and clomipramine exerted more pronounced effects than UP 614-04 on hemodynamic parameters. However, all three agents had qualitatively similar dose–response characteristics in that low doses produced slight increases in systolic blood pressure and heart rate, intermediate doses did not alter haemodynamic parameters, and high doses produced marked cardiodepressor effects. Imipramine and clomipramine were also much more potent than UP 614-04 in potentiating the pressor action of intravenously administered norepinephrine. Taken together, these results have indicated that UP 614-04 is about five times less cardiotoxic and about four to eight times less potent as a cardiodepressor than imipramine or clomipramine.     

Investigation of the orthostatic reaction after intravenous administration of imipramine,chlorimipramine, and imipramine-N-oxide

Three age- and sex-matched groups of 10 patients were treated intravenously with imipramine, chlorimipramine, and imipramine-N-oxide, respectively, in increasing doses from 25 mg to 150–175 mg given as single daily infusions during 1 hour. No systemic changes of heart frequency and blood pressure were found during the infusions in spite of the high dosage of tricyclic antidepressants given in such a short period as 1 hour. The patients were examined regarding orthostatic reactions as well as ECG changes before, after 4–5 infusions and after 8–10 infusions. There were more orthostatic abnormalities and ECG changes in the patients treated with imipramine than in those treated with imipramine-N-oxide and there were practically no changes in the chlorimipramine group. However, no statistically significant orthostatic changes were found.     

Action of antidepressants,stimulants and depressants in the transition from a fixed ratio to a fixed interval schedule of reinforcement

1. The modifications of rat behaviour caused by imipramine, amitriptyline, doxe pin, amphetamine, chlorpromazine, caffeine and diazepam were studied.2. The schedule of reinforcement was changed from a fixed ratio to a fixed interval schedule.3. All the studied drugs caused a depression of the rat behaviour but only tricyclic antidepressants and caffeine caused virtually no damage to the ability of the animal to adapt its behaviour to the new experimental situation.     

Effects of Imipramine on Behavior and Brain Norepinephrine Metabolism in Tetrabenazine Treated Rats: Comparative Study of a Single Administration with Repeated Administrations of Imipramine

Abstract: The effects of a single and repeated administrations of imipramine on the tetrabenazine-induced sedation in rats were studied. The 3-methoxy-4-hydroxyphenylethyleneglycol-sulfate (MHPG-SO₄) level in the brain was measured. 1) A single administration of imipramine of 20 mg/kg had no significant effect on the rats' locomotor activity and the brain MHPG-SO₄. The administration of 30 mg/kg of tetrabenazine produced marked sedation and significantly increased the brain MHPG-SO₄. 2) The imipramine pretreatment reversed the tetrabenazine-induced sedation. The brain MHPG-SO₄ in the rats treated with a single administration of imipramine along with tetrabenazine decreased significantly, compared with that in the rats treated with tetrabenazine only. The administration of α-methyl-para-tyrosine (α-MT) of 250 mg/kg suppressed the reversal of the tetrabenazine-induced sedation. The administration of Ro4-4602 of 50 mg/kg and L-3,4-dihydroxyphenylalanine (L-DOPA) of 100 mg/kg had no significant effect on the reversal. 3) The repeated daily administrations of imipramine of 20 mg/kg reversed the tetrabenazine-induced sedation and produced the locomotor hyperactivity. When the rats were treated with the repeated administrations of imipramine for five days and had tetrabenazine administered on the last day, the brain MHPG-SO.J increased significantly as compared with that in the rats treated with a single administration of imipramine and tetrabenazine. There was no difference in the amount of locomotor activity between the rats administered imipramine of 20 mg/kg and tetrabenazine and those administered imipramine of 40 mg/kg and tetrabenazine. 4) Several considerations were given to the above-mentioned results.