DNA damage in children treated with imipramine for primary nocturnal enuresis

BACKGROUND: Despite the fact that primary nocturnal enuresis (PNE) is self-limited and pathologically benign, the emotional stress and inconvenience that it produces, warrants treatment. Imipramine is one of the widely used drugs in PNE treatment. Although some mutagenic effects were suggested in imipramine administration, this toxicity has never been investigated in enuretic patients. The aim of this study was to evaluate the association of exposure to imipramine with DNA damage. METHODS: Thirty-five children treated with imipramine for at least 4.5 months who were in otherwise good health were accepted into the investigation. Twenty healthy sisters or brothers of the patients who did not use any long-term drugs were studied simultaneously as the control group. Comet assay was used to evaluate DNA damage. RESULTS: Damaged (limited and extensive migrated) cells of the enuretic children who were taking imipramine were statically higher than that of the control group (P < 0.05) indicating a detectable DNA damaging effect of imipramine in human lymphocytes. CONCLUSIONS: Our finding suggests that the difference in comet scores between two groups was induced by the imipramine treatment. The other possibility to be considered is the psychological stress of the children who were concerned by the symptoms and their parent's anxiety. As our preliminary data were based on a limited number of children, further research is needed considering the importance of this possible toxic effects which may be associated with mutagenicity.     

Localization of GABAA and GABAB receptor subtypes on serotonergic neurons

The effect of selective destruction of serotonin (5-HT)-containing neurons with 5,7-dihydroxytryptamine (5,7-DHT) on [3H] muscimol and (-)-[3H]baclofen binding was investigated in various rat brain regions. Ten days after intracerebroventricular 5,7-DHT, serotonin levels and [3H]imipramine binding were markedly decreased. 5,7-DHT reduced [3H]muscimol binding only in the mesencephalon, and (-)-[3H]baclofen binding was unmodified in all the areas considered. These results suggest that except in the mesencephalon GABA receptors may not be localized on serotonergic nerve terminals.     

路优泰治疗老年抑郁症20例

目的观察路优泰治疗老年抑郁症的临床疗效与安全性。方法将符合《中国精神障碍分类与诊断标准第三版(CCMD-3)》抑郁症诊断标准的老年抑郁症患者43例随机分为两组,A组20例,给予路优泰600～900 mg/d治疗,B组23例,给予丙咪嗪50～200 mg/d治疗,疗程均为6周,疗效和副反应分别采用汉密尔顿抑郁量表(HAMD)和副反应量表(TESS)进行评定。结果 A组总有效率为70.00%,B组为78.26%,两组比较差异无统计学意义(P>0.05);A组TESS评分显著低于B组(P<0.01)。结论路优泰是一种安全有效的抗抑郁药,适用于老年抑郁症。     

Central nervous system depressant activity of an ethyl acetate extract from Ipomoea stans roots

Ipomoea stans Cav., popularly known as "tumbavaqueros", is a plant widely used in Mexico for the treatment of epileptic seizures and nervous disorders. This work researched the action of the ethyl acetate extract from the root of I. stans (IS-EAE) on the central nervous system (CNS). The administration of IS-EAE (2.5 and 5.0 mg/kg, i.p.) produced an anxiolytic effect in mice. This extract (20.0 and 40.0 mg/kg, i.p.) significantly reduced spontaneous motor activity. 2.5, 5.0, 10.0, and 20.0 mg/kg of IS-EAE protected mice against pentylenetetrazole-induced convulsions and increased the hypnotic effect induced by pentobarbital. The administration of IS-EAE was able to increase the release of GABA in brain cortex of mice. These results suggest that IS-EAE possess anxiolytic and anticonvulsant effects, and could have potential sedative effect, probably through a GABAergic system. The extract did not show antidepressant effects on mice exposed to forced swimming test.     

Effects of imipramine and mirtazapine on operant performance in rats

The effects of the tricyclic antidepressant imipramine and the atypical antidepressant mirtazapine were compared on the performance of rats in three operant procedures: a differential reinforcement of low rates schedule (DRL), a delayed matching to position (DMTP), and simultaneous visual discrimination tasks. Both compounds improved performance in the DRL task in a similar dose-related manner. Imipramine, but not mirtazapine, disrupted performance in the visual discrimination task. Imipramine reduced accuracy and increased response latencies and missed trials. Neither compound effected accuracy in the DMTP; both compounds caused some slowness of responding and imipramine caused several animals to fail to respond in a manner similar to that observed in the visual discrimination task. These data suggest that although imipramine and mirtazapine are similarly effective in putative tests of antidepressant activity, imipramine has a greater tendency to disrupt other aspects of cognitive performance, as well as exert generally depressive effects on operant responding.     

Normalizing effect of antidepressant imipramine on changes in circadian movement pattern of pinealectomized rats after a change in timing of the period of daylight

Department of Pharmacology, Stavropol' Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR D. A. Kharkevich.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 12, pp. 595–597, December, 1991.     

Hypoxia activates glycogen synthase kinase-3 in mouse brain in vivo: protection by mood stabilizers and imipramine.

BACKGROUND: Glycogen synthase kinase-3 (GSK3), which is primarily regulated by an inhibitory phosphorylation of an N-terminal serine, has been implicated as contributing to mood disorders by the finding that it is inhibited by the mood stabilizer lithium. METHODS: This study tested if the antidepressant imipramine or the mood stabilizers lithium and sodium valproate regulated pathophysiological serine-dephosphorylation of GSK3 caused by hypoxia in mouse brain in vivo. RESULTS: Hypoxia caused rapid serine-dephosphorylation of both isoforms of GSK3, GSK3beta and GSK3alpha, in mouse cerebral cortex, hippocampus, and striatum. Pretreatment of mice with imipramine, sodium valproate, or lithium attenuated hypoxia-induced serine-dephosphorylation of GSK3beta and GSK3alpha in all three brain regions. CONCLUSIONS: These results demonstrate that imipramine and mood stabilizers are capable of blocking pathophysiologically induced serine-dephosphorylation of GSK3, supporting the hypothesis that stabilization of serine-phosphorylation of GSK3 contributes to their therapeutic effects.     

Aggression, hyperactivity and platelet imipramine binding.

We measured platelet 3H-imipramine binding parameters in 16 subjects affected by different types of mental deficiency, all characterized by hyperactive and/or aggressive behaviour, and in 16 healthy controls. The patients had a lower maximum binding capacity than the controls, with no difference in Kd, irrespectively of the type of mental disorder. These findings suggest a link between 5-HT disturbances, reflected by reduced imipramine binding sites, and behavioural dyscontrol, expressed as hyperactivity and aggression.     

Drug treatment of panic disorder: early response to treatment as a predictor of final outcome

One of the core problems in clinical research is the detection of early changes in target symptoms that predict future therapeutic outcome. To analyze potential predictors of outcome, data of a multicenter study on patients with panic disorder were used. A total of 1010 patients were randomly allocated either to alprazolam, imipramine or placebo treatment. Early improvement in the number of spontaneous panic attacks within the first week of treatment predicted outcome exclusively in the alprazolam group. In contrast, placebo responders and nonresponders were differentiated by early changes in anticipatory anxiety intensity. For tricyclic antidepressants such as imipramine an evaluation period of more than one week is required to allow conclusions about outcome.     

Overcoming resistance to exposure in panic disorder with agoraphobia

The issue of panic disorder resistant to treatment (whether pharmacological or psychological) has attracted little research attention, despite its clinical frequency and importance. The aim of this study was to compare three treatment modalities, namely exposure alone (E), exposure associated with imipramine (EI) and cognitive therapy supplementing exposure (EC), in a sample of 21 patients with DSM-IV panic disorder and agoraphobia, who failed to respond to a first standard course of individual behavioural treatment based on exposure in vivo. Treatments were administered according to a cross-over, controlled design (E-EI-EC, EI-EC-E, EC-E-EI). Twelve of the 21 patients achieved remission (panic-free status) during the trial. In 8 cases this occurred after exposure alone (E) and in two cases each after the other treatments (EI and EC). The results revealed a significant effect of the factor time on a number of variables, and the superiority of exposure alone compared to other treatment modalities with regard to some variables. These findings suggest that long-term behavioural treatment based on exposure may be necessary in some patients, and may induce clinical remission. However, patients who do not respond to exposure show poor tolerance of and compliance with pharmacological treatment, and are unlikely to achieve remission with imipramine or cognitive therapy, even though this may occur in individual cases.