Imipramine protects retinal ganglion cells from oxidative stress through the tyrosine kinase receptor B signaling pathway

Retinal ganglion cell（RGC） degeneration is irreversible in glaucoma and tyrosine kinase receptor B（Trk B）-associated signaling pathways have been implicated in the process.In this study,we attempted to examine whether imipramine,a tricyclic antidepressant,may protect hydrogen peroxide（H_2O_2）-induced RGC degeneration through the activation of the Trk B pathway in RGC-5 cell lines.RGC-5 cell lines were pre-treated with imipramine 30 minutes before exposure to H_2O_2.Western blot assay showed that in H_2O_2-damaged RGC-5 cells,imipramine activated Trk B pathways through extracellular signal-regulated protein kinase/Trk B phosphorylation.TUNEL staining assay also demonstrated that imipramine ameliorated H_2O_2-induced apoptosis in RGC-5 cells.Finally,Trk B-Ig G intervention was able to reverse the protective effect of imipramine on H_2O_2-induced RGC-5 apoptosis.Imipramine therefore protects RGCs from oxidative stress-induced apoptosis through the Trk B signaling pathway.

Effects of Imipramine and Lithium on the Expression of Hippocampal Wnt 3a and Cyclin D1 in ACTH-Treated Rats

We have shown previously that chronic administration of adrenocorticotropic hormone (ACTH) causes a significant decrease in hippocampal cell proliferation and neurogenesis. This effect in rats treated chronically with ACTH was not influenced by the chronic administration of imipramine, but was reversed by coadministration of imipramine and lithium. The present study was undertaken to further characterize the mechanism underlying the effect of imipramine and lithium on hippocampal cell proliferation and neurogenesis, by investigating the effects of treatment on the expression of brain-derived neurotrophic factor (BDNF), total cyclic adenosine monophosphate response element-binding protein (CREB), and phosphorylated CREB (pCREB) of the CREB signaling system, as well as Wnt 3a and cyclin D1 of the Wnt signaling pathway in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1. Treatment with imipramine and lithium increased the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF, CREB, pCREB, and Wnt 3a did not change in either saline-treated or ACTH-treated rats. These findings suggest that the antidepressant effect of imipramine and lithium in ACTH-treatment-resistant rats may be attributed, at least in part, to an enhancement of cyclin D1 expression.

Modulation of Anxiolytic-Like and Antidepressant-Like Effects of Melatonin by Imipramine in Wistar Rats: Possible Interaction with Central Monoaminergic Systems

Our current study aims to explore the interaction of melatonin (MEL) with the monoaminergic system on the pathophysiology of affective disorders in Wistar rats. We mention here that, the role of monoaminergic transmission in the pathophysiology of affective disorders in humans is demonstrated in most recent reports. In this sense, our current work aims to explore the effect of melatonin (MEL) with or without imipramine (IMP) on levels of depression and anxiety in Wistar rats and would determine the role of MEL in modulating serotonin, noradrenaline and dopamine neurotransmission. From this point, twenty-four female Wister rats were divided into 4 groups of 6 animals and received subcutaneously during 4 weeks different doses of MEL (4 mg/kg), IMP (2 mg/kg) or MEL (4 mg/kg) + IMP (2 mg/kg). Behavioral performance especially anxiety and depression is measured in the open field (OFT), elevated plus maze (EPM) and forced swim test (FST). The anxiety-like and antidepressant-like effects were observed with MEL at 4 mg/Kg and IMP at 2 mg/Kg but the potentiating effect was more observed with the two combined molecules (MEL and IMP), since locomotors activity assessed by the OFT and EPM was not affected. These effects suggest that psychopharmacological actions of MEL are due, at least in part, to its ability to potentiate the central monoaminergic transmitter effects.

Imipramine Inhibits Adipogenic Differentiation in Both 3T3-L1 Preadioocvtes and Mouse Marrow Stromal Cells

Imipramine （IM） has been widely used clinically for the treatment of mental disorders. Its actions on tissues or organs other than the nervous system also need to be understood for its proper clinical use. In this study, the effects of IM on adipogenic differentiation in both 3T3-L1 preadipocytes and mouse marrow stromal cells （MSCs） were investigated. The results showed that fewer adipocytic cells were developed from 3T3-L1 preadipocytes in the presence of 0.001 to 1 μmol/L of IM as compared to control. Similar inhibitory effect was also observed in mouse MSCs. The decrease in the formation of adipocytes was accompanied with significant down-regulation at mRNA expression of the early adipogenic transcription factor, peroxisome proliferator-activated receptor γ2 （PPARγ2）. Western blot analysis further revealed that the protein expression of PPARγ2 was reduced markedly in ceils treated with IM at concentrations of 0.01, 0.1 and 1 μmol/L, suggesting that the suppression on PPAR72 was involved in IM＇s inhibition on MSCs adipogenesis. Moreover, IM at the above concentrations could stimulate the mRNA expression of β2-adrenergic receptor （AR） and β3-AR, which implicated that the effect of IM on adipogenic differentiation was partially mediated by β-ARs. Our results demonstrated for the first time that the conventional antidepressive imipramine exerts accompanied inhibitory effect on adipocyte formation, which may have possible clinical implications.

Management of nocturnal enuresis-myths and facts

Nocturnal enuresis often causes considerable distress or functional impairment to patient and their parents necessitating a multidisciplinary approach from paediatrician, paediatric nephrologist, urologists and psychiatrist. Mechanisms of monosymptomatic nocturnal enuresis are mainly nocturnal polyuria, bladder overactivity and failure to awaken from sleep in response to bladder sensations. Goal oriented and etiology wise treatment includes simple behavioral intervention, conditioning alarm regimen and pharmacotherapy with desmopressin, imipramine and anticholinergic drugs. Symptoms often recurs requiring change over or combination of different modes of treatment.

Failure of memantine to “reverse” quinpirole-induced hypomotility

AIM: To evaluate antidepressant-like effect of memantine in a rat model.METHODS: Male Wistar rats were treated intraperitoneally with either vehicle, memantine(10 mg/kg) or imipramine(20 mg/kg), for 3 wk. Twenty-four hour after the last treatment animals were challenged with quinpirole(0.3 mg/kg s.c.) and tested for motor activity. After 1 h habituation to the motility cages, the motor response was recorded for the following 45-min and the data were collected in 5-min time bins. RESULTS: As expected, chronic treatment with imipramine potentiated the locomotor stimulant effect of quinpirole. On the contrary, chronic memantine administration failed to induce the behavioral supersensitivity to the dopamine agonist. CONCLUSION: The results show that memantine, at variance with antidepressant treatments, fails to induce dopaminergic behavioral supersensitivity. This observation is consistent with the results of preclinical and clinical studies suggesting that memantine does not have an acute antidepressant action but does have an antimanic and mood-stabilizing effect.

Role of serendipity in the discovery of classical antidepressant drugs:Applying operational criteria and patterns of discovery

The role played by serendipity in the origin of modern psychopharmacology has proven to be controversial in scientific literature.In its original meaning(Walpole),serendipity refers to discoveries made through a combination of accidents and sagacity.We have implemented an operational definition of serendipity based on finding something unexpected or unintended,regardless of the systematic process that led to the accidental observation,and we have established four different patterns of serendipitous attributability.In this paper,we have analyzed the role of serendipity in the discovery and development of classical antidepressant drugs,tricyclic antidepressants and monoamine oxidase inhibitors as well as heterocyclic,“atypical”or“second generation”antidepressants.The discovery of the antidepressant properties of imipramine and iproniazid,the prototypes of tricyclic antidepressants and monoamine oxidase inhibitors,respectively,fits the mixed type II pattern;initial serendipitous discoveries(imipramine was an antipsychotic and iproniazid was an antituberculosis agent)led secondarily to non-serendipitous discoveries.But the other components of these two families of drugs were developed specifically as antidepressants,modifying the chemical structure of the series leaders,thereby allowing all of them to be included in the type IV pattern,characterized by the complete absence of serendipity.Among the heterocyclic drugs,mianserin(originally developed as an antihistamine)also falls into the type II pattern.

The Effect of Neurofeedback Therapy in Primary Enuretic Children

Introduction:?Enuresis is one of the most common psychiatric disorders in children. Classical?treatments for primary enuretic children are conditioning (Bell and Pad method, and drug therapy). Neurofeedback is a kind of conditioning by changing amplitudes of brain waves. Method: Three?groups of 10 enuretic children were selected randomly. All three groups took imipramine. The?first group also took neurofeedback sessions with protocol of enhancement of?β/θ?wave ratio in occipital zone. The second group took non-real neurofeedback sessions beside the drug. The third?group just took the drug. Result:?All three groups showed significant remission (P < 0.0001) after treatment and a three-month follow-up. Conclusion:?Neurofeedback by this protocol was not any more efficient than imipramine therapy by itself.