抗抑郁药物治疗幽门螺旋杆菌阴性的慢性胃炎临床观察

目的:探讨抗抑郁药物对幽门螺旋杆菌阴性的慢性胃炎的治疗作用.方法:将298例幽门螺旋杆菌阴性的慢性胃炎患者随机分成对照组和治疗组,对照组140例予以奥美拉唑胶囊治疗,治疗组158例予以奥美拉唑胶囊及抗抑郁药物(氟哌噻吨美利曲辛片)联合治疗4周,然后对两组治疗前后的疗效进行分析.结果:两组治疗后患者的症状改善程度差异有显著性.结论:抗抑郁药物联合质子泵抑制剂对改善幽门螺旋杆菌阴性的慢性胃炎的症状有显著效果,可作为幽门螺旋杆菌阴性的慢性胃炎有效治疗途径之一.     

Acute effects of antidepressant drugs on long-term potentiation (LTP) in rat hippocampal slices

Summary The actions of three clinically effective antidepressant drugs with different pharmacological profiles were investigated in the CAI area of rat hippocampal slices. Imipramine and (+) or (–)-oxaprotiline had negligible effects on population spikes evoked by stratum radiatum stimulation, but reduced postsynaptic excitability in low Ca high Mg medium after an exposure of more than 15 min. Imipramine and (+)-oxaprotiline at 10 mol/l enhanced long-term potentiation (LTP) when a lower stimulation strength was applied while (+)-oxaprotiline reduced UP when a higher stimulus amplitude was used to evoke population spikes. (–)-oxaprotiline (levoprotiline) had a similar effect which was, however, not significant in either stimulation paradigm at the P<0.05 level. Imipramine actions were also studied on epileptiform discharges in Mg²⁺-free medium: a facilitation-inhibition sequence with a slow time course was seen with 50 mol/l but no effect with 10 mol/l. An involvement of N-methyl-D-aspartate (NMDA)-receptors in acute actions of antidepressants is unlikely but long-term potentiation in the hippocampus is modulated by these drugs. Send offprint requests to H.L. Haas, Düsseldorf     

抗抑郁药物的作用机理与研究进展

本文通过查阅国内外有关文献,对抗抑郁症药物的作用机理与研究进展进行阐述,为抗抑郁药物的进一步研究提供参考。     

The use of antidepressant drugs in general practice

Summary The aim of this study was to examine the antidepressant drug prescribing preferences and habits of a population of general practitioners. The method used was that of a questionnaire survey, including case vignettes. The response rate exceeded 70% Data are presented outlining the attitudes of the respondents to the use of antidepressant drugs in the management of common psychiatric presentations in the primary care setting.The majority of general practitioners (G.P.'s) had received little or no post-graduate education in psychiatry. The antidepressants most frequently prescribed were amitriptyline, clomipramine, trazodone and lofepramine. Despite recognition of the alarming frequency of serious self-poisoning incidents with some of these compounds, 26% of respondents confessed to an inability to make an informed choice of antidepressant drug, with 14% using the same drug with every patient with no attempt to select according to individual patient requirements.The management of depressive neurosis generates considerable clinical confusion with a variety of interventions favoured. The use of a sedating antidepressant is popular. There is greater accord for the management of endogenomorphic depression. The use of the benzodiazepine drugs in the management of anxiety disorders is infrequent, with appropriate recognition of the merits of behavioural approaches. However, the role for antidepressant drugs in the management of anxiety disorders is under-recognized.We conclude that general practitioners are required to undertake a significant body of work for which they may be inadequately trained.     

Effect of antidepressant drugs on serotonergic and adrenergic receptors

Summary We examined eight tricyclic antidepressants (doxepin, amitriptyline, clomipramine, imipramine, trimipramine, nortriptyline, desipramine and protriptyline) and four nontricyclic antidepressants (mianserin, nomifensin, iprindole and zimelidine) in terms of their effects on serotonergic and adrenergic receptors by direct binding assays.³H-WB-4101 (0.22 nM) served as a label for postsynaptic alpha receptors while³H-clonidine (0.2 nM) served to label presynaptic alpha receptors in the frontal cortex of the calf.³H-dihydroalprenolol (³H-DHA) (0.5 nM) was used to label the beta₁ adrenoceptors in the calf frontal cortex and beta₂ adrenoceptors in the calf cerebellar cortex.³H-d-Lysergic acid diethylamide (³H-LSD) (2 nM) and³H-serotonin (³H-5HT) (0.5 nM) were used to label the serotonergic receptors in the calf frontal cortex.The results show that at drug concentrations which occur clinically in the plasma water, most of the tertiary amine tricyclics significantly inhibited³H-WB-4101,³H-LSD and³H-5HT binding. None of the antidepressants tested had any significant effect on³H-DHA binding. The secondary amine tricyclics as a group were not potent in inhibiting the binding of all four radiolabelled ligands. The nontricyclic antidepressant mianserin was potent in inhibiting the binding of³H-WB-4101,³H-clonidine,³H-LSD and³H-5HT. We suggest that the differences between the effects of the antidepressants on adrenergic and serotonergic receptors may be responsible for the differences in their therapeutic efficacies and side effects.Supported by the Canada Medical Research Council and the Ontario Mental Health FoundationA preliminary report of this work was presented at the 9th annual meeting of the Society for Neuroscience, Atlanta, 1979     

Cyclodextrins improving the physicochemical and pharmacological properties of antidepressant drugs: a patent review

Introduction: Depression is a serious mood disorder and is one of the most common mental illnesses. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these drugs, which have a slow onset of action in addition to producing undesirable side effects. Some scientific evidence suggests that cyclodextrins (CDs) can improve the physicochemical and pharmacological profile of antidepressant drugs (ADDs). The purpose of this paper is to disclose current data technology prospects involving antidepressant drugs and cyclodextrins.

Areas covered: We conducted a patent review to evaluate the antidepressive activity of the compounds complexed in CDs, and we analyzed whether these complexes improved their physicochemical properties and pharmacological action. The present review used 8 specialized patent databases for patent research, using the term ‘cyclodextrin’ combined with ‘antidepressive agents’ and its related terms. We found 608 patents. In the end, considering the inclusion criteria, 27 patents reporting the benefits of complexation of ADDs with CDs were included.

Expert opinion: The use of CDs can be considered an important tool for the optimization of physicochemical and pharmacological properties of ADDs, such as stability, solubility and bioavailability.     

Serotonin-mimetic and antidepressant drugs on passive avoidance learning by olfactory bulbectomised rats

Olfactory bulbectomised rats were treated with drugs and their rate of acquisition of a passive avoidance task was measured. The acquisition-rate, which is disturbed by the bilateral ablations, was completely restored by acute administration of fenfluramine or fluoxetine. Partial restoration was found with quipazine. Clonodine was without effect. Repeated treatments with impramine and mianserine improved passive avoidance of bulbectomised rats. Metergoline blocked these effects of imipramine and mianserin. These results indicate a serotonergic mechanism in the effect of antidepressants on olfactory bulbectomised rats.     

The acute effects of antidepressant drugs on the performance of conditioned avoidance behavior in rats

The effects of acute administration of 10 different antidepressant drugs were examined on the performance of a two-way conditioned avoidance response in rats. The antidepressant drugs impaired avoidance behavior by decreasing avoidance responding and increasing the number of escape failures. The order of effectiveness for increasing overall response latency at a common dose of 10 mg/kg was: desipramine, maprotiline, protriptyline, (+) oxaprotiline, nortriptyline, imipramine, amitriptyline, (-) oxaprotiline, fluoxetine, and chlorimipramine. Avoidance behavior was impaired most by those antidepressant drugs that are also potent inhibitors of norepinephrine uptake.     

The influence of central noradrenergic function on 5-HT2-mediated head-twitch responses in mice: Possible implications for the actions of antidepressant drugs

This study has investigated the influence of central noradrenergic function on 5-HT₂-mediated head-twitch responses in mice. Central injection of low doses of the α₁-adrenoceptor agonists phenylephrine or methoxamine, or peripheral administration of the antagonist prazosin had no effect on the head-twitches induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). High doses of both α₁-adrenoceptor agonists and antagonists markedly inhibited this response. Head-twitches induced by 5-MeODMT were potently inhibited by low doses of the α₂-adrenoceptor agonist clonidine, and potentiated by the antagonists idazoxan and yohimbine. Clonidine also potently inhibited this response when produced by 5-hydroxytryptophan (5-HTP) and carbidopa. The action of the β-adrenoceptor agonist clenbuterol on head-twitches was paradoxical, this drug enhancing the responses to precursor loading (5-HTP/carbidopa) but inhibiting those induced by direct agonists (5-MeODMT, quipazine). Lesioning noradrenergic neurons by central injection of 6-hydroxydopamine (6-OHDA) or peripheral administration of DSP-4 resulted in enhanced head-twitch behaviour. 6-Hydroxydopamine lesioning did not alter the inhibition of head-twitch responses by clonidine but prevented their enhancement following withdrawal from repeated desmethylimipramine (DMI) administration. It is therefore suggested that head-twitch behaviour may be under tonic control by a population of α₂-adrenoceptors which are not on presynaptic noradrenergic terminals, but are postsynaptic and located “down-stream” of the 5-HT₂ receptor. In addition, the enhancement of this behaviour produced by withdrawal from repeated DMI administration probably also resulted from alterations in central noradrenergic function.     

Reduced peripheral presynaptic adrenoceptor sensitivity following chronic antidepressant treatment in rats.

In view of the recent M1 and M2 subclassification of muscarinic receptors and the suggestion of separate populations of muscarinic receptors on oxyntic and histamine cells in the gastric mucosa, we have analysed the effects of McN-A 343, classified as an M1-selective agonist, on gastric acid secretion by the mouse, isolated, lumen-perfused stomach assay. Acid secretion stimulated by McN-A 343 was not inhibited by tetrodotoxin pretreatment, although it was competitively antagonized by atropine (pKB 7.90), suggesting a muscarinic site of action between postganglionic neurones and the final secretory event. Acid secretion stimulated by McN-A 343 was more sensitive than 5-methylfurmethide-stimulated secretion to H2-receptor blockade: the profile of inhibition was consistent with expectations for a model of indirect agonism, suggesting that McN-A 343 preferentially stimulated the release of endogenous histamine from mucosal histamine cells. In view of this selective action the McN-A 343-pirenzepine interaction was studied, the latter being classified as an M1-selective antagonist. Results were consistent with expectations for a competitive interaction but the pKB (6.69) was not significantly different from the value obtained at the oxyntic cell, using 5-methylfurmethide as agonist in the presence of H2-receptor blockade, in a previous study. We suggest that there is no need to postulate differences in oxyntic and histamine cell muscarinic receptors to account for the selective stimulant activity of McN-A 343 observed in this study and the relatively selective inhibition of gastric acid secretion by pirenzepine in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition effects of some antidepressant drugs on pentose phosphate pathway enzymes

The glucose metabolism in the pentose cycle is essential to the source of NADPH. Deficiency of these enzymes have been linked to depression and psychotic disorders. Depression is an increasingly prevalent mental disorder which may cause loss of labor. Antidepressant drugs are commonly employed in treatments of mood disorders and anxiety treatment. The purpose of this study is to investigate the effects of aripiprazole, mirtazapine, risperidone, escitalopram and haloperidol on the activity of 6-phosphogluconate dehydrogenase (6PGD) and glucose-6-phosphate dehydrogenase (G6PD) enzymes purified from human erythrocytes. It was found that aripiprazole, mirtazapine, risperidone, escitalopram and haloperidol show effective inhibitor properties on purified G6PD and 6PGD enzymes. The IC₅₀ values of these drugs were found in the range of 26.34 μM-5.78 mM for 6PGD and 16.26 μM-3.85 mM for G6PD. The K_i values of the drugs were found in the range of 30.21 ± 4.31 μM-4.51 ± 1.83 mM for 6PGD and 14.12 ± 3.48 μM-4.98 ± 1.14 mM for G6PD. Usage of drugs with significant biological effects may be a hazard in some conditions.     

Metabolism of 5-hydroxytryptamine and levels of tricyclic antidepressant drugs in rat brain after acute and chronic treatment

Because tricyclic antidepressants (TAD) are usually given chronically to patients, both their acute and their chronic effects on 5-hydroxytryptamine (5-HT) metabolism were studied. The probenecid method was used and, in addition to 5-hydroxyindoleacetic acid (5-HIAA), some other indole compounds in brain were measured. Simultaneously, TAD levels in brain and plasma were determined. Dimethylated as well as monomethylated TADs were administered, both at 10 and 25 mg/kg i.p.Treatment with either 10 mg/kg during 14 days or 25 mg/kg given acutely resulted in a similar brain level of TAD, so any differences found could be attributed to differences in administration schedule. Drug levels in brain and plasma differed considerably after chronic and acute treatments but no major differences in the effect on 5-HIAA level in the brain were found, although accumulation of 5-HIAA following probenecid treatment was mostly lowered after treatment with dimethylated TAD. The TAD level in rat brain was not decisive for the effect on central 5-HT turnover. The monomethylated TAD affected the 5-HT turnover very little, not only acutely but also chronically.     

Alpha 2-adrenoreceptors on human platelets: selective labelling by [3H]clonidine and [3H]yohimbine and competitive inhibition by antidepressant drugs

[3H]Clonidine and [3H]yohimbine have been used to characterize alpha 2-adrenoreceptors on human platelets. At 25 degrees C binding was rapid (t 1/2 of association, 1.8 and 2.7 min) and reversible (t 1/2 of dissociation, 0.5 and 8.2 min). The binding sites for [3H]clonidine and ]3H]yohimbine showed the specificity required for an alph 2-adrenoreceptor. The rank order of potency of inhibitors of [3h[clonidine binding was clonidine greater than yohimbine greater than phenylephrine greater than prazosin and of [3H]yohimbine binding was yohimbine greater than clonidine greater than phenylephrine greater than prazosin. Scatchard analysis of [3H]yohimbine binding indicated the existence of a single population of noninteracting sites (KD = 3.0 nM; Bmax = 188 fmol/mg protein). The high-affinity binding of [3H-clonidine had a lower affinity and a lower number of sites (KD = 5.0 nM; Bmax = 35 fmol/mg protein). [3H]Clonidine binding also showed evidence of a second site of much lower affinity and greater number (KD = 18.6 nM; Bmax = 77 fmol/mg protein) in 40% of the normal population. In vitro, antidepressant drugs competed with [3H]clonidine and [3H]yohimbine for the platelet alpha 2-adrenoreceptor. The rank order of potency of inhibitors of [3H]clonidine binding was mianserin greater than amitriptyline greater than iprindole greater than desipramine and of [3H]yohimbine binding was mianserin greater than amitriptyline greater than desipramine greater than iprindole. The inhibition constants (Ki) of adrenergic drugs and of various antidepressant drugs in competing with [3H]clonidine were correlated with the inhibition constants of these drugs in competing with [3H]yohimbine (r = 0.970; P less than 0.001) which suggests that both radioligands labelled the same alpha 2-adrenoreceptor on the human platelet. The inhibition of binding induced by all antidepressant drugs was competitive. In contrast, long-term administration of tricyclic antidepressant drugs to patients was recently found to be associated with a decrease in the number of binding sites for [3H]clonidine on platelet membranes. The present results indicate that both [3H]clonidine and [3H]yohimbine are useful tools for the quantification of alpha 2-adrenoreceptors on blood platelets and suggests that the specific binding of radiolabelled alpha 2-adrenoreceptor ligands to human platelet membranes might be used to monitor changes in alpha 2-adrenoreceptors during tricyclic antidepressant drug treatment.     

Co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex induced by clozapine,the prototype atypical antipsychotic

Rationale. Clozapine has been shown to increase extracellular dopamine (DA) and noradrenaline (NA) in the medial prefrontal cortex (mPFC). A recent study of ours suggested that extracellular DA in the PFC originates not only from dopaminergic but also from noradrenergic terminals, its release being controlled by α₂-adrenoceptors. Objectives. Since clozapine binds to α₂-adrenoceptors, the possibility that it might co-release DA and NA was studied. Methods. By means of microdialysis coupled to HPLC with electrochemical detection, the effect of clozapine on extracellular DA and NA in the mPFC, densely innervated by DA and NA, was compared to that in the occipital cortex, equally innervated by NA but receiving few DA projections. Results. Extracellular NA was found to be the same in the two cortices, consistent with homogeneous NA innervation. On the other hand, extracellular DA in the occipital cortex was only 29% lower than in the mPFC, in spite of the scarce dopaminergic innervation in the occipital cortex. Clozapine (10 mg/kg IP) increased extracellular DA and NA not only in the mPFC (by about 320% and 290%, respectively) but also in the occipital cortex (by 560% and 230%, respectively). Administration of the α₂-agonist clonidine (0.15 mg/kg) reversed the effect of clozapine in both cortices, while the D₂-agonist quinpirole (0.1 mg/kg IP) was ineffective. Conclusions. The results suggest that clozapine, by inhibiting α₂-adrenoceptors, co-releases DA and NA from noradrenergic terminals in the occipital cortex and that the same mechanism might be responsible for the concomitant increase of the two monoamines in the mPFC. Electronic Publication     

Facilitated shock-induced aggression after chronic treatment with antidepressant drugs in the rat

The effects of four antidepressant drugs with different mechanisms of action on shock-induced fighting between pairs of rats were determined. Amitriptyline, imipramine, mianserin and iprindole, given chronically, facilitated fighting behavior     

Facilitation by GABA of the potassium-evoked release of 3H-noradrenaline from the rat occipital cortex

Summary The effects of GABA were studied on the release of ³H-noradrenaline (³H-NA) evoked by potassium or by tyramine from slices of the rat occipital cortex and on the release of ³H-NA elicited by nerve stimulation from the cat nictitating membrane.GABA (30–1000M) facilitated the potassium-evoked release of ³H-NA in a concentration dependent manner. This facilitatory effect was not antagonized by bicuculline (1–100 M) or by picrotoxin (1–100 M). Exposure to the GABA agonist muscimol (1–100 M) did not affect either the spontaneous or the potassium-evoked release of ³H-NA.The facilitatory effect of GABA on the release of ³H-NA elicited by potassium was observed when the occipital cortex slices were exposed to 20 mM K⁺ during 1 min. When depolarization was induced by 35 mM K⁺ exposure to GABA failed to enhance the release of the neurotransmitter. GABA 300 M did not affect the release of the labelled neurotransmitter evoked by exposure to tyramine 0.6 M.In the cat nictitating membrane prelabelled with ³H-NA, the stimulation evoked release of the labelled neurotransmitter was not affected by GABA (10–300 M).In conclusion, GABA has a facilitatory effect on the calcium-dependent, potassium evoked release of ³H-NA when the depolarization is of moderate degree. This effect of GABA appears to be selective for the central nervous system.Some of the findings described in this paper have been presented at the Meeting of the British Pharmacological Society (March, 1978, Guildford, U.K.)     

Repeated treatment with antidepressant drugs prevents salbutamol-induced hypoactivity in rats

We have found earlier that a number of antidepressant drugs, administered repeatedly, prevent the salbutamol-induced hypoactivity in rats. Our further experiments show that a similar effect is produced by repeated, but not acute, treatment with other antidepressants: clomipramine, mianserin and nialamide. Two non-antidepressant psychotropic drugs, haloperidol and diazepam, were inactive after repeated administration. These results seem to support our earlier hypothesis that prevention of the salbutamol-induced hypoactivity may be regarded as functional evidence at the behavioral level for the subsitivity of beta-adrenoceptors.     

Combination of antidepressant drugs: the case of inositol

Inositol is a second messenger precursor that is effective in depression and obsessive-compulsive disorder via a mechanism different from serotonin reuptake inhibitors. However, controlled trials of inositol combined with serotonin reuptake inhibitors in depression or in reuptake inhibitor resistant depressed patients, or in partially responsive obsessive-compulsive patients, did not reveal added benefit. This is comparable to results with combinations of other antidepressant treatments, such as tricyclics plus monoamine oxidase inhibitors. Copyright 2001 John Wiley & Sons, Ltd.     

抗抑郁治疗对高血压伴抑郁症患者血压和生活质量的影响

[目的]探讨抗抑郁药物西酞普兰联合心理康复对高血压并抑郁症患者血压和生活质量的影响.[方法]106例伴有抑郁障碍的原发性高血压患者随机分为对照组和观察组各53例,对照组予常规治疗,观察组在对照组的基础上加用抗抑郁药物西酞普兰联合心理康复治疗,观察两组患者治疗前后血压、抑郁症状与生活质量的变化情况.[结果]治疗6周后,观察组总有效率为92.45％,对照组为71.70％,差异有显著性(P＜0.05);两组患者的收缩压、舒张压及HAMD评分均较治疗前明显下降(P＜0.05),观察组下降幅度明显大于对照组(P＜ 0.05);观察组患者治疗后躯体功能、心理功能、社会功能、物质功能及生活质量总分均明显升高(P＜0.05),对照组治疗前后变化不明显(P＞0.05).[结论]对原发性高血压病伴有抑郁症患者在常规治疗的基础上给予抗抑郁药物治疗与心理康复,能有效改善患者的生活质量,明显提高患者血压控制率.