Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DESIPRAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,603 records · Page 89Linked to original sources
PubMed1990

Antidepressant or antianxiety? A study of the efficacy of antidepressant medication.

The authors analyzed the relative contributions of improvement in depressive and anxiety symptoms, as measured by the Hamilton Rating Scale for Depression (HRSD) and the Hamilton Rating Scale for Anxiety (HRSA), respectively, after 1 week of treatment to the prediction of improvement in HRSD score after 6 weeks of antidepressant pharmacotherapy. Fifty-six subjects completed 6 weeks of treatment with either desipramine (n = 20), alprazolam (n = 18), or a desipramine-alprazolam combination (n = 18). The results showed that early improvement in the HRSD was a moderately strong predictor of the total 6-week improvement in HRSD score, and a better predictor than early improvement in the HRSA. Partial correlations showed that early HRSD improvement was significantly related to total HRSD improvement within the alprazolam group. This pattern of response differed from those observed for the other treatment groups. Desipramine-treated subjects showed gradual improvement over the course of the study, and the improvement in week 1 was not so strongly predictive of overall improvement. The relationship between early and total HRSD improvement for the combination treatment group was intermediate to the other two groups. These findings are discussed in the context of the relationship between depression and anxiety, and potential implications for the treatment of these overlapping and often mixed syndromes.

Adult↗
PubMed1993

Effects of antidepressant drug treatment on levels of NPY or prepro-NPY-mRNA in the rat brain.

The effects of acute and chronic treatment with the tricyclic antidepressant drugs, imipramine, clomipramine and desipramine on levels of neuropeptide Y (NPY) and prepro-NPY-mRNA were studied in different areas of the rat brain. Chronic treatment with imipramine (6.3-25 mg/kg/day) for 10-30 days caused an approx. 15-25% reduction in NPY immunoreactivity in the frontal cortex, but only insignificant changes in striatum, hippocampus, amygdala and hypothalamus. Slight and insignificant changes in the concentrations of prepro-NPY-mRNA were also detected by Northern blot analysis in these brain areas. Only in the hypothalamus was a 20% increase in prepro-NPY-mRNA found. NPY or prepro-NPY-mRNA levels were not altered 3 or 24 h after a single injection of imipramine. The effects of clomipramine and desipramine, at doses of 25 mg/kg daily for 10 days, were investigated in the frontal cortex and in the hippocampus. Except for a slight decrease in prepro-NPY-mRNA in the frontal cortex after desipramine no significant changes in NPY tissue levels or prepro-NPY-mRNA concentrations were observed in the frontal cortex and the hippocampus. In summary, treatment with the three tricyclic antidepressant drugs had no consistent effects on the brain NPY system. These data do not support the previous suggestion that antidepressant drugs may exert their actions by increasing NPY levels in the brain.

Animals↗
PubMed1995

REM latency, dexamethasone suppression test, and thyroid releasing hormone stimulation test in posttraumatic stress disorder.

1. Twenty-one patients with post-traumatic stress disorder (PTSD) were included in a study utilizing baseline rapid eye movement (REM) latency measurements, the dexamethasone suppression test (DST), and the protirelin (thyroid releasing hormone; TRH) stimulation test. The DST and TRH stimulation test were repeated after double blind treatment with desipramine. 2. A high number of patients (75%) exhibited a REM latency of 60 min or less and blunted thyroid stimulating hormone (TSH) response to TRH (61.9%) on baseline tests while only one patient showed cortisol escape from dexamethasone suppression. 3. After four weeks of desipramine treatment, significant improvements were reported in the Hamilton Rating Scale for depression, but not for anxiety symptoms, PTSD symptoms, or self-rated depressive symptoms. 4. Desipramine treatment did not affect hormonal responses to TRH. 5. The findings of shortened REM latency and altered TRH stimulation test suggest PTSD and depression may share some pathophysiological abnormalities.

Adult↗
PubMed1986

Quantification of the dopamine innervation in adult rat neostriatum.

Conditions leading to specific and integral visualization of dopamine axon terminals (varicosities) were tested in adult rat cerebral hemisphere slices incubated with [3H]dopamine and processed for high resolution radioautography. Specific visualization of the dopamine endings was achieved after incubation with 10(-6) M [3H]dopamine in the presence of a monoamine oxidase inhibitor (pargyline 10(-4) M), and of desipramine (5 X 10(-6) M), an inhibitor of catecholamine uptake by noradrenaline and serotonin neurons. [3H]Dopamine varicosity labeling was eliminated by the addition of 5 X 10(-5) M benztropine (an inhibitor of catecholamine uptake by catecholamine neurons), and was almost absent when dopamine nerve cell bodies of the midbrain had been previously destroyed with 6-hydroxydopamine. In dopamine-denervated neostriatum incubated without desipramine, a second set of labeled terminals was also visible. These were identified as serotoninergic, since their labeling was suppressed by citalopram, an inhibitor of monoamine uptake highly specific for serotonin neurons. There was no desipramine-sensitive but citalopram-resistant varicosity labeling suggestive of neostriatal noradrenaline innervation. In normal striatum, incubation at 35 degrees C always resulted in a labeling of dopamine varicosities restricted to a narrow band which followed the contours and cut surface of this anatomical region. This unusual distribution was the result of an uptake barrier generated by the tightly packed dopamine varicosities. Indeed, the striatal dopamine varicosity labeling was more widespread after partial 6-hydroxydopamine denervation or in normal tissue incubated either with a higher [3H]dopamine concentration (5 X 10(-6) M), in the presence of relatively low benztropine concentrations (10(-5) M), or at lower temperature (15 degrees C). Material incubated at 15 degrees C for 90 min was suitable for purposes of quantification: labeled varicosities were then visualized throughout the striatum and across the full thickness of the slices; moreover, the number of labeled varicosities plotted against radioautographic exposure time increased in parallel and reached a plateau at the same time in neostriatal sectors with widely different innervation densities. At a rostral transverse level across neostriatum, the dorsolateral quadrant showed hyperdense "patches" of labeled terminals distinguishable from an already dense surrounding "matrix", whereas, ventromedially, the dopamine innervation appeared more uniform and somewhat less dense.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

The study of tricyclic antidepressants in formalin-fixed human liver and formalin solutions.

The stability of amitriptyline, nortriptyline, desipramine and imipramine in formalin-fixed human liver tissue and formalin solutions was investigated. The levels of the tricyclic and its primary demethylated metabolite in the frozen liver were determined and compared with levels obtained in the formalin-fixed liver and formalin solutions in which the liver was stored. It was obvious that some methylation of the secondary amine, nortriptyline, to the corresponding tertiary amine, amitriptyline, and of desipramine to imipramine took place in the formalin environment. Nortriptyline was not detected in most cases, suggesting that it may degrade more rapidly than desipramine. There was no consistent ratio between the concentration of the drug in the frozen liver tissue versus formalin-preserved tissue or versus formalin solution. The methylation rates of the secondary amines could not be quantitated. Storage of the liver tissue in formalin at room temperature resulted in leaching of the drugs into the formalin solution. The drugs tested may be detected for up to 22 months in the formalin-fixed liver and in the formalin medium.

Amitriptyline↗
PubMedDate not supplied

Effect of low alcohol dose on behavioral "despair" in rats neonatally treated with antidepressant drugs.

Rat pups were treated with monoamine uptake inhibiting antidepressant drugs, desipramine, imipramine or nomifensine (5 mg/kg) during the second and third postnatal weeks, and their later behavioral "despair," measured by Porsolt's swim test, was examined. At the age of two months, the desipramine-treated rats showed lengthened immobility in the swim test, and thus probably increased behavioral "despair." They also responded to 1 g/kg alcohol by shortening the immobility to the level of control rats. Neonatal treatment with either imipramine or nomifensine did not affect the swim test behavior. The results suggest that a low, stimulatory dose of alcohol was able to reverse the lengthened immobility in the swim test of rats treated with desipramine during the early postnatal period.

Animals↗
PubMed2006

Neuronal proteins involved in synaptic targeting of AMPA receptors in rat hippocampus by antidepressant drugs.

Recent data suggest that the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subtype plays a pivotal role in the pathogenesis of effective disorders and in the action of antidepressant drugs. After chronic treatment with the antidepressants desipramine or paroxetine, we measured by immunoprecipitation and Western blotting, the changes in the interaction of AMPA receptor subunits with proteins involved in trafficking and/or stabilization of the subunits into synaptic membranes of the hippocampus. Both antidepressants increased the interaction of GluR1 subunit with stargazin and of GluR2/3 with NSF. Paroxetine increased the interaction of GluR1 with Rab4A, and desipramine markedly increased the interaction of GluR1 with SAP97. Paroxetine, but not desipramine, also increased membrane levels of CaMKII, autophosphorylated CaMKII and GluR1 phosphorylated at the CaMKII site. Interactions of GluR1 and GluR2/3 with proteins implicated in AMPA receptor trafficking and with scaffolding proteins appear to account for the enhanced membrane expression of AMPA receptors in the hippocampus after antidepressant treatment.

Animals↗
PubMed2006

Characterization of cytotoxic actions of tricyclic antidepressants on human HT29 colon carcinoma cells.

Preclinical studies have suggested that the long-term use of antidepressants may result in the initiation and/or promotion of tumor in the gastrointestinal tract. However, a possible relationship between the use of antidepressants and the production of colon cancer has not yet been confirmed, and hence requires to be further investigated. To address this issue, the effects of antidepressants on the proliferation of colorectal tumor cells were examined using human HT29 colon carcinoma cells, and tricyclic antidepressant, such as imipramine, desipramine and amitriptyline, were shown to reduce the cell viability in a manner dependent on the time exposing to these drugs. In addition to these drugs, a selective serotonin reuptake inhibitor fluoxetine, but not a monoamine oxidase inhibitor tranylcypromine, caused the reduction of cell viability, similar in extent to that caused by imipramine. Further studies showed that desipramine caused the apoptotic cell death, which could be prevented by neither catalase, reduced-form glutathione (GSH), nor N-acetylcysteine (NAC), without accompanying the disruption of mitochondrial membrane potential within the cells and the release of cytochrome c into the cell cytoplasm. Moreover, desipramine caused the arrest of cell-cycle progression at either G0/G1-phase or G2/M-phase, which might be depending upon the drug concentration. Thus, these results suggest that tricyclic antidepressants may be cytotoxic, and induce the non-oxidative apoptotic death of human HT29 colon carcinoma cells probably through a non-mitochondrial pathway associated with the cell-cycle progression.

Amitriptyline↗
PubMed2006

The comparison of immobility time in experimental rat swimming models.

Rat swimming models have been used in studies about stress and depression. However, there is no consensus about interpreting immobility (helplessness or adaptation) in the literature. In the present study, immobility time, glucose and glycogen mobilization, corticosterone and the effect of desipramine and diazepam were investigated in two different models: swimming stress and the forced swimming test. Immobility time was lower in swimming stress than in the forced swimming test. Both swimming models increased corticosterone levels in comparison with control animal levels. Moreover, swimming stress induced higher corticosterone levels than the forced swimming test did [F(2,14)=59.52; p<0.001]. Liver glycogen content values differed from one another (swimming stress<forced swimming test<control), [F(2,17)=32.08; p<0.001]. The glycogen content values in the gastrocnemius [F(2,16)=11.35; p=0.026] and soleus [F(2,16)=8.68; p=0.006] muscles were lower during swimming stress in comparison with the forced swimming test and control. The immobility time was recorded and measured in another group treated with desipramine and diazepam in two protocols: a single session of forced swimming test or swimming stress and two sessions (pre- and retest) of forced swimming model or swimming stress. Desipramine decreased the immobility time in the forced swimming test in both the single [F(2,25)=20.63; p<0.0001] and retest [F(2,37)=7.28; p=0.002] swimming session, without changes in the swimming stress model. Diazepam increased the immobility time in the swimming stress but not in the forced swimming test during the single [F(2,26)=11.24; p=0.0003] and retest sessions [F(2,38)=4.17; p=0.02]. It was concluded that swimming stress and the forced swimming test induced different behavior, hormonal and metabolic responses and represented different situations to the animal.

Animals↗
PubMed2004

Regulation of the norepinephrine transporter by chronic administration of antidepressants.

BACKGROUND: Downregulation of serotonin transporter was observed previously after chronic treatment with selective serotonin reuptake inhibitors (SSRIs) but not selective norepinephrine reuptake inhibitors (NRIs). This study investigated if chronic treatment of rats with selective NRIs or SSRIs also affected the norepinephrine transporter (NET). METHODS: Rats were treated for 3 to 6 weeks by osmotic minipumps with either the selective NRIs, desipramine, or the SSRI paroxetine. RESULTS: [(3)H]nisoxetine binding sites as well as [(3)H]norepinephrine uptake were decreased in hippocampus and cortex after treatment with desipramine. By contrast, paroxetine-treated rats showed no alteration in either [(3)H]nisoxetine binding or [(3)H]norepinephrine uptake. NET messenger RNA levels in the locus coeruleus were unchanged by desipramine treatment. CONCLUSIONS: These results demonstrate that the marked decrease in NET density 1) is not a consequence of a decrease in gene expression; 2) was caused only by a selective NRI; and 3) was associated with a parallel decrease in norepinephrine uptake.

Adrenergic Uptake Inhibitors↗
PubMed1996

Reduction of substance P after chronic antidepressants treatment in the striatum, substantia nigra and amygdala of the rat.

We investigated the effects of chronic treatment with food containing one of five antidepressants on substance P (SP) content in the rat brain using radioimmunoassay and enzyme-immunoassay. The antidepressants used were imipramine, desipramine, clomipramine, amoxapine and mianserin. Following 40 days of treatment, all the antidepressants decreased SP concentrations in the striatum, substantia nigra and amygdala. Only imipramine and desipramine reduced the peptide content in the hippocampus, and only mianserin reduced it in the septum. We further examined the acute effects of antidepressants one hour after a single intraperitoneal administration. Acute imipramine and desipramine treatment reduced SP in the striatum, whereas acute mianserin decreased it in the striatum and substantia nigra. These results demonstrate that all antidepressants on chronic treatment had a common effect, a reduction of SP content in the striatum, substantia nigra and amygdala. This raises the possibility that such a decrease may contribute to the therapeutic action of antidepressants in affective disorders.

Amoxapine↗
PubMed2001

Myocardial interstitial norepinephrine and dihydroxyphenylglycol levels during ischemia and reperfusion.

OBJECTIVE: The aim was to elucidate the relation between norepinephrine (NE) release and intraneuronal NE kinetics in the ischemic region of the in vivo heart. METHODS: Using dialysis technique in the heart of anesthetized cats, we sampled dialysate from the ischemic region during 120-min coronary occlusion and reperfusion. Dialysate NE and dihydroxyphenylglycol (DHPG) contents were measured as indexes of myocardial interstitial NE and DHPG levels. RESULTS: Within 20 min of occlusion, interstitial NE levels increased while DHPG levels decreased. This NE increase was suppressed by omega-conotoxin GVIA and enhanced by desipramine. These data suggest that axoplasmic NE levels increased by neuronal reuptake following exocytotic release, while intraneuronal DHPG production was suppressed due to the reduced monoamine oxidase activity. After 20 min of occlusion, interstitial NE levels increased markedly, accompanied by increased DHPG levels. This NE increase was suppressed by desipramine. These findings imply that NE mobilization from stored vesicles to axoplasma exceeded outward NE transport through uptake(1) carrier in the amount of NE, and that a substantial increase in axoplasmic NE levels compensated for the reduced monoamine oxidase activity. After reperfusion, interstitial NE levels rapidly decreased while DHPG levels increased further. Both responses in NE and DHPG were suppressed by desipramine, indicating the involvement of recovered neuronal reuptake function. CONCLUSIONS: In the ischemic region, intraneuronal DHPG production was affected by alterations in monoamine oxidase activity, NE mobilization from stored vesicles, and carrier-mediated NE transport. The involvement of these factors in intraneuronal NE kinetics varied with the time of occlusion and reperfusion.

Animals↗
PubMed2001

Group housing of mice increases immobility and antidepressant sensitivity in the forced swim and tail suspension tests.

The forced swim test and tail suspension test are often used in laboratory practice to identify compounds that possess antidepressant-like activity. This experiment was conducted to determine whether housing conditions per se influence the response of mice in these antidepressant screening procedures. Male NIH Swiss mice were housed individually or in groups (five per cage) for 8 weeks prior to testing. After 8 weeks, the animals were exposed to the forced swim and tail-suspension tests. Group housed mice displayed high levels of immobility in the forced swim and tail suspension tests. Desipramine injection 60 min prior testing, in doses 7.5 and 15 mg/kg, produced significant reductions in the immobility time in forced swimming and tail suspension tests. Individually housed mice, when exposed to these tests, displayed lower levels of immobility with a magnitude comparable to the effect of desipramine in group housed mice. Desipramine given to individually housed mice did not reduce the duration of immobility either in the forced swim test or in the tail suspension test. These results indicate that both tests are sensitive to housing conditions. This observation suggests that long lasting group housing may be critical to the behavioral response in these preclinical screening procedures in mice.

Animals↗
PubMed1997

Tricyclic antidepressants block cholinergic nicotinic receptors and ATP secretion in bovine chromaffin cells.

Nicotine-induced ATP secretion from chromaffin cells was blocked by imipramine and desipramine. This blocking action took place on both, fast and slow, components of ATP secretion. Exposure of chromaffin cells to nicotine (10 microM) for 4 s induced an inward current of about -155 pA. Imipramine and desipramine blocked, in a concentration-dependent manner, both peak inward current and total charge influx in response to nicotine. In addition, imipramine and desipramine partially (40%) blocked depolarization-induced ATP secretion and Ca2+ currents evoked by high K+. This suggests that tricyclic antidepressants block nicotine-induced ATP secretion by acting on two targets: one is the nicotinic receptor itself and the second one are voltage-dependent Ca2+ channels.

Adenosine Triphosphate↗
PubMed2001

A possible indirect sympathomimetic action of metformin in the arterial vessel wall of spontanously hypertensive rats.

The antidiabetic drug metformin (MF) typically achieves only micromolar levels in plasma with normal therapeutic use. However, it is also known to accumulate in various tissues up to several times higher after standard oral dosing and we now have evidence from both in vivo and in vitro experiments with spontaneously hypertensive rats (SHR) that millimolar levels stimulate release of norepinephrine (NE) from vascular sympathetic nerve endings (SNEs). As shown in the present work with SHR tail arterial tissue (rich in SNEs), the known vasodilator effect of millimolar levels of MF on the smooth muscle (even if contracted with a nonadrenergic agonist), is attenuated by the presence of the SNEs unless phentolamine (an alpha receptor blocker) is present. We reasoned that the mechanism for this apparent NE-releasing action of MF is not exocytotic release as that would require depolarization of the neuronal cell membranes in SNEs, and MF at millimolar levels is known to repolarize (not depolarize) membranes of other cells. Thus, we tested the possibility that MF releases NE by an indirect sympathomimetic-like action. Such an action should be amplified by monoamine oxidase inhibitors (e.g. iproniazid) and blocked by NE-carrier inhibitors (e.g. desipramine). Accordingly, we found that the abovementioned attenuating effect of intact SNEs on MF's relaxation of SHR tail arterial tissue (compared to tissues in which SNEs were experimentally removed with 6-hydroxydopamine) was amplified nearly 3-fold by iproniazid (p<0.05) and blocked by desipramine (p<0.05). These results support an indirect sympathomimetic action of MF and raise the question whether commonly used antidepressants with properties similar to iproniazid and desipramine might alter MF's beneficial vasodilatory (and thus antihypertensive) effectiveness in diabetic patients with hypertension.

Animals↗
PubMed1999

5-Hydroxytryptamine inhibits the tachycardia induced by selective preganglionic sympathetic stimulation in pithed rats.

It has been shown in several species that serotonin (5-hydroxytryptamine; 5-HT) is able to inhibit the responses produced by sympathetic stimulation in a wide variety of blood vessels and other organs, including the heart. However, in pithed rats, the analysis of potential sympatho-inhibitory actions of 5-HT is hampered by the fact that 5-HT (given as i.v. bolus injections) produces tachycardia per se. Moreover, most studies have investigated 5-HT-induced sympatho-inhibition at only one frequency of stimulation. Thus, the present study set out to find the experimental conditions to overcome these problems. In this regard, we analyzed the potential ability of 5-HT, administered as i.v. continuous infusions, to inhibit the tachycardia caused by stimulation of the preganglionic (C7-T1) sympathetic outflow in pithed rats. Sympathetic cardiostimulation (0.01-3 Hz) resulted in frequency-dependent increases in heart rate; these responses were potentiated after desipramine (50 microg/kg, i.v.). During continuous infusions of 5-HT (3.1-10 microg/kg.min, i.v.), but not saline, the sympathetically-induced tachycardia was dose-dependently inhibited in both control and desipramine-pretreated rats. This inhibitory effect of 5-HT was significantly more pronounced at lower frequencies of stimulation. In contrast, the above infusions of 5-HT did not inhibit the tachycardia induced by i.v. bolus injections of noradrenaline in both control and desipramine-pretreated rats. Taken together, the above findings confirm that 5-HT induces inhibition of the sympathetic chronotropic outflow in the rat by acting at receptors located prejunctionally, without evoking tachycardia, over a wide range of stimulation frequencies.

Animals↗
PubMed1999

Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat.

In the present study we observed that lipopolysaccharide (LPS) administration provoked a characteristic reduction in body weight gain, food consumption, saccharin (but not water) consumption and nocturnal locomotor activity. It has been previously suggested that the ability of LPS to suppress the consumption of, and preference for, a palatable solution such as saccharin without altering water consumption, may represent an anhedonic response. The results of the present study demonstrate that chronic treatment with the tricyclic antidepressant (TCA) desipramine (7.5 mg/kg; i.p.) prevented LPS-induced anorexia, loss of body weight, the antidipsogenic effect and hypoactivity. In contrast, chronic treatment with the antidepressants paroxetine (7.5 mg/kg; i.p.) and venlafaxine (10 mg/kg; i.p.) failed to alter any of the LPS-induced behavioural responses. Furthermore, chronic treatment with desipramine (and to a lesser extent paroxetine) reduced the consumption of, and preference for, saccharin suggesting that these antidepressant treatments induce an "anhedonic" response in their own right. In conclusion, chronic desipramine treatment attenuated LPS-induced depressive-like behavioural symptoms in the rat. However, chronic treatment with paroxetine and venlafaxine did not significantly alter LPS-induced behavioural responses. The results of the present study support the hypothesis that TCA's may exert part of their anti-depressive efficacy through their effects on the immune system. However, this property does not appear to be shared by newer antidepressants which possess a better side effect profile than the TCA's. The suppressive effect of TCA's on proinflammatory cytokine secretion is discussed as a mechanism by which these agents alter LPS-induced behavioural responses.

Adrenergic Uptake Inhibitors↗
PubMed2000

Effect of subchronic antidepressant treatments on behavioral, neurochemical, and endocrine changes in the forced-swim test.

The purpose of the present study was to examine the effect of subchronic treatment (24 days) with antidepressants displaying differential effects on noradrenaline and serotonin reuptake, on behavior, neurochemistry, and hypothalamic-pituitary-adrenal (HPA) axis activity following FST exposure in the rat. Desipramine (7.5 mg/kg, IP) significantly decreased immobility in the FST, whilst paroxetine (7.5 mg/kg IP) and venlafaxine (10 mg/kg, IP) were without effect. Nonetheless, treatment with all three antidepressants significantly attenuated stress-related increases in amygdaloid and cortical serotonin turnover. Of the three antidepressants examined, only desipramine attenuated the stress-associated elevation in serum corticosterone. In conclusion, although FST-induced increases in serotonin turnover in the frontal cortex and amygdala were attenuated following treatment with all three antidepressants, FST-induced behavioral changes and increased HPA axis activity were normalized only following desipramine treatment. In addition, these results suggest that neurochemical mechanisms independent of increased serotonergic activity subserve the normalization of behavior and HPA axis responses in the FST. These data also add to our understanding of the interactions between antidepressants and stress-induced behavioral, neurochemical, and endocrine alterations, and illustrates important differences between classes of antidepressants.

Amygdala↗