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Results for “DESIPRAMINE”

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PubMed1999

Six months of desipramine for dysthymia: can dysthymic patients achieve normal social functioning?

BACKGROUND: There is evidence that antidepressant medication improves social dysfunction during acute treatment in dysthymic patients but it is unknown if the gain in social functioning persists or progresses with longer-term antidepressant treatment. We examine the effect of 6 months of desipramine treatment on social functioning in dysthymic patients. METHODS: Forty-six subjects with DSM-III-R dysthymia (70% with superimposed major depression) who had responded to 10 weeks of open-label desipramine (DMI) treatment received 16 additional weeks of continuation DMI. Social functioning was measured at weeks 0, 10 and 26 with the Social Adjustment Scale-Self Report. RESULTS: Euthymia was maintained and a marginally significant trend for further improvement in overall social functioning appeared during continuation treatment. Only 24% of subjects achieved normative level of social adjustment after 6 months of DMI treatment. LIMITATIONS: The main limitation was the lack of a placebo control group. CONCLUSION: Acute improvement in social functioning persists during continuation treatment. However, most dysthymic patients did not achieve a community level of social adjustment. Significant social dysfunction persists in dysthymic patients with low levels of depressive symptomatology after 6 months of intense DMI treatment.

Adult↗

PubMed2002

Sister chromatid exchanges produced by imipramine and desipramine in mouse bone marrow cells treated in vivo.

Imipramine and desipramine are two widely used tricyclic antidepressants which have shown conflicting results in regard to their in vitro genotoxic evaluation. The aim of this investigation was to determine the capacity of these compounds to induce in vivo sister-chromatid exchanges (SCEs) in mouse bone marrow cells. For each compound, the animals were organized in five groups constituted by five individuals. They were intraperitoneally (ip) administered with the test substances as follows: a negative control group treated with 0.4 ml of distilled water, a positive control group administered with cyclophosphamide (70 mg/kg), three groups treated with imipramine (7, 20 and 60 mg/kg), and three other groups treated with desipramine (2, 20 and 60 mg/kg). The general procedure included the subcutaneous implantation to each mouse of a 5-bromodesoxyuridine tablet (45 mg), and 1 h later, the administration of the chemicals involved. Twenty-one hours after the tablet implantation, the mice received colchicine, and 3 h later their femoral bone marrow was obtained in KCL, fixed, and stained with the Hoechst-Giemsa method. The results showed that both compounds were SCE inducers, starting from the second tested dose. The response of these compounds was dose-dependent, and showed that the highest tested dose increased about four times the SCE control level. The cellular proliferation kinetics was not affected by the chemicals, and the mitotic indexes were slightly diminished with the highest dose. These results indicate an in vivo genotoxic potential for both chemicals, and suggest that it is pertinent to follow their evaluation in other models.

Animals↗

PubMed1988

Simultaneous determination of imipramine, desipramine and their deuterium-labelled analogues in biological fluids by capillary gas chromatography-mass spectrometry.

A specific, sensitive and accurate method for the determination of imipramine, desipramine and their d4 analogues in biological fluids using d8 analogues as internal standards using capillary gas chromatography-chemical ionization mass spectrometry was developed. Drug concentrations were measured by selected-ion monitoring of the quasi-molecular ions of imipramine and the trifluoro-acetyl derivative of desipramine. The coefficient of variation and relative error at a concentration of about 2 ng/ml in plasma were found less than 10% and 7%, respectively, for both drugs. No isotope effect was observed following the oral administration of an equimolar mixture of imipramine and [2H4]imipramine to a rat.

Animals↗

PubMed1997

Simultaneous determination of imipramine, desipramine and their 2- and 10-hydroxylated metabolites in human plasma and urine by high-performance liquid chromatography.

A simultaneous assay for imipramine, desipramine and their 2- and 10-hydroxy-metabolites using high-performance liquid chromatography (HPLC) is described. The drugs and internal standard, pericyazine, were extracted from plasma or urine at pH 9.6 with diethyl ether and back-extracted into 0.1 M orthophosphoric acid. The recovery of the compounds ranged from 78.6% for imipramine to 94.3% for 2-hydroxydesipramine. The extracts were analysed by reversed-phase HPLC with electrochemical detection using a mobile phase of 30% acetonitrile in 0.1 M K2HPO4 at pH 6.0 delivered at 2 ml/min. All compounds were resolved in a run time of 15 min with lower limits of quantification of 1.5 ng/ml for hydroxy-metabolites and 3 ng/ml for imipramine and desipramine. The intra- and inter-day coefficients of variation at 50 ng/ml were 5.2% and 6.8%, respectively (n=8).

Adult↗

PubMed2000

Spectrophotometry assay of imipramine and desipramine using ammonium metavanadate and its application to pharmaceutical preparations.

Simple and sensitive method for determination of imipramine and desipramine is reported. The procedure is based on the oxidation of the drugs by ammonium metavanadate. Linear calibration graphs were obtained in the concentration range 0.6-40 microg ml(-1) of imipramine and 0.7-35 microg ml(-1) of desipramine with a relative standard deviation (RSD) less than 0.5%. The method was applied to the determination of the drugs in pharmaceutical preparations and compared favourably with independent official methods.

Antidepressive Agents, Tricyclic↗

PubMed2000

Effects of propofol on desipramine-sensitive [3H]-noradrenaline uptake kinetics in rat femoral artery.

BACKGROUND: The intravenous anaesthetic propofol inhibits the neuronal uptake of noradrenaline (uptake1) from the vascular sympathetic neuromuscular junction, resulting in an enhancement of the sympathetic neurotransmission. This could be important for maintenance of blood pressure during propofol anaesthesia. The aim of the present study was to determine how propofol influences the kinetics of uptake1. METHODS: Isolated segments of rat femoral arteries were incubated with [3H]-noradrenaline in the presence or absence of propofol and the radioactivity taken up was measured in a scintillation counter. The uptake1 inhibitor, desipramine, was used to delineate the specific neuronal uptake. RESULTS: Desipramine and 10 microM propofol significantly reduced the uptake in segments incubated with 0.1 microM [3H]-noradrenaline. Propofol at 1 microM and 100 microM did not affect the uptake. Non-linear regression analysis of specific uptake yielded Km 0.50 microM, Vmax 1.6 pmol mg(-1) 15 min(-1) and Hill coefficient 1.1. Propofol (1-10 microM) increased the Km value and propofol (10-100 microM) increased the Vmax value concentration-dependently, while the Hill coefficient was not affected. CONCLUSION: Propofol seems to have a biphasic effect on the uptake of noradrenaline in the vascular sympathetic neuromuscular junction. At lower propofol concentrations there is a decrease in the affinity of the noradrenaline transporters. The resulting uptake inhibition is counteracted at higher propofol concentrations by an increase in the efficacy of the uptake.

Adrenergic Uptake Inhibitors↗

PubMed1992

Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population.

The molecular basis of polymorphic debrisoquin hydroxylation was studied in 223 Swedish white subjects, 187 extensive metabolizers and 36 poor metabolizers phenotyped with debrisoquin and desipramine. Restriction fragment length polymorphism (RFLP) analysis of the CYP2D6 gene revealed that 52% of unrelated poor metabolizers were homozygous for Xba I 29 kb fragment, and only 8% had two mutant alleles detected with RFLP. Allele-specific polymerase chain reaction (PCR)-based DNA amplification, however, revealed that all but one of the poor metabolizers had two mutant alleles of the CYP2D6A or CYP2D6B type or both. Extensive metabolizers who were heterozygous for wild-type and CYP2D6B genes had metabolic ratios for debrisoquin and desipramine that were higher than those of subjects who were homozygous for the wild-type gene. The 16 + 9 kb Xba I RFLP pattern was associated with the poor metabolizer phenotype and CYP2D6B mutations. Three extremely rapid metabolizers of debrisoquin had a 44 kb Xba I fragment that did not carry either CYP2D6A or CYP2D6B mutations. In conclusion, in the Swedish population studied, allele-specific PCR amplification allowed prediction of the debrisoquin hydroxylation phenotype with 99% accuracy.

Adolescent↗

PubMed1998

Blockade of 5-hydroxytryptamine and noradrenaline uptake by venlafaxine: a comparative study with paroxetine and desipramine.

1. Venlafaxine is an antidepressant agent which blocks in vitro the reuptake of both 5-HT and NA. The present in vivo electrophysiological studies were undertaken, in the rat, to compare the effects of venlafaxine on 5-HT and NA reuptake to those of the selective 5-HT reuptake inhibitor paroxetine and the selective NA reuptake inhibitor desipramine. 2. Administered acutely, venlafaxine dose-dependently prolonged the time required for a 50% recovery (RT50) of the firing activity of dorsal hippocampus CA3 pyramidal neurons from the suppression induced by microiontophoretic applications of 5-HT and NA. Venlafaxine and paroxetine increased with a similar potency the RT50 values for 5-HT, while desipramine was more potent than venlafaxine at increasing the RT50 values for NA. Moreover, venlafaxine demonstrated a greater potency at increasing the RT50 values for 5-HT compared to that of NA. 3. A two-day treatment with venlafaxine (delivered s.c. by osmotic minipumps) increased the RT50 values for both 5-HT and NA applications. The RT50 values for 5-HT were significantly increased at a dose of 10 mg kg(-1) day(-1), whereas those for NA were increased at a dose of 20 mg kg(-1) day(-1), consistent with the data obtained following the acute administration of venlafaxine. 4. Taken together, these results indicate that, in vivo, venlafaxine blocks both reuptake processes, with a potency greater for the 5-HT than for the NA reuptake process. This dual action, combined with the differential potency of venlafaxine, might constitute the biological substratum responsible for its apparent unique clinical efficacy in major depression.

Adrenergic Uptake Inhibitors↗

PubMed1999

Different effect of desipramine on protein kinase C in platelets between bipolar and major depressive disorders.

Protein kinase C (PKC) activity was investigated in platelets from affective disorder subjects and healthy volunteers. The PKC activity of platelets incubated with desipramine was determined in vitro. The PKC activity of the major depressive disorder subjects and healthy volunteers was inhibited by desipramine, whereas that of the bipolar disorder subjects showed both inhibition and activation. In addition, the base PKC activity incubation with antidepressants of the major depressive disorder patients was significantly higher than of the bipolar disorder patients. These preliminary results suggest that the function of PKC may, at least in part, be associated with the mechanism of affective disorder.

Adult↗

PubMed1992

Platelet alpha 2-adrenergic receptors in depressed patients and healthy volunteers: the effects of desipramine.

Binding parameters (Bmax and Kd) of alpha 2-adrenergic receptors were studied in platelets from 14 depressed patients and 18 control subjects. Using 3H-clonidine (a partial alpha 2-adrenergic agonist) as the ligand and membranes, prepared from platelets isolated under physiological conditions, we found no significant differences in Bmax and Kd between medication free patients and control subjects. Platelet binding parameters in the depressed patients did not correlate with plasma levels of norepinephrine, epinephrine or MHPG. Age had a significant positive effect on platelet alpha 2-adrenergic receptor Bmax in both groups, and may have masked the patient-control differences. Treatment with desipramine for 28 days had no effect on the binding parameters in depressed patients when compared to pretreatment values. Adding desipramine to platelets of control subjects 'in vitro' did also not affect binding parameters. Our findings suggest that receptor binding studies with a partial alpha 2-adrenergic agonist in platelet membranes are not a useful model to test the hypothesis of a central supersensitive adrenergic system in depression.

Analysis of Variance↗

PubMed2005

Chronic treatment with clomipramine and desipramine induces deficit in long-term visuo-spatial memory of rats.

Although the effects of antidepressants in brain neurochemistry have been extensively studied, there are scarce and inconsistent data on the effect of these drugs in learning and memory. The authors studied the effect of daily administration of a single dose of either clomipramine or desipramine, two monoamine-reuptake-inhibitors with preferential serotonergic and noradrenergic profiles, respectively, during 15 days, on the visuo-spatial memory of adults rats measured through their performance in an eight-arm radial maze. Rats receiving 10 mg/kg i.p. daily of clomipramine or desipramine, 30 min before testing, committed a significantly greater number of errors than saline-treated control rats throughout the duration of the test (5 sessions, 15 days), excepting for session one (after 3 days of testing) where there were no differences between the 3 groups of rats. Results indicated that both serotonergic and noradrenergic antidepressants could impair long-term visuo-spatial memory in the rat, whereas inducing no changes in working memory, effects that are likely related to changes in brain monoamine metabolism induced by the antidepressant drugs.

Analysis of Variance↗

PubMed2003

Comorbid major depressive disorder as a prognostic factor in cocaine-abusing buprenorphine-maintained patients treated with desipramine and contingency management.

Depression is common among patients who abuse both opiates and cocaine, and its treatment has had mixed success. This study compares buprenorphine-maintained patients with lifetime major depressive disorder (MDD, N = 53) with those never depressed (ND, N = 96) on cocaine and opiate-free urines during a 12-week outpatient double-blind, placebo-controlled, randomized clinical trial. The 149 subjects were assigned to four groups: 1) desipramine (DMI) + contingency management (CM); 2) DMI + noncontingency management (NCM); 3) placebo + CM; and 4) placebo + NCM. Depression assessments included Hamilton Depression Rating Scale, Center for Epidemiological Studies Depression Inventory, and Structured Clinical Interview for DSM-IV interview for diagnosis of lifetime MDD. Urine toxicologies were performed thrice weekly and the CES-D was performed monthly. The MDD group had a larger proportion of females (45% vs 21%, P = 0.02) and were more likely to be married (13.2% vs 7.3%, P = 0.02) than the ND group. Treatment retention did not vary by depression status. Hierarchical Linear Modeling found that depressive symptoms decreased comparably across the four treatment groups. Although participation in CM improved drug-free urines more for patients with MDD than for the ND group (Z = 2.44, P = 0.01), treatment with DMI was significantly more efficacious for the ND group than for the MDD group (Z = -2.89, P = 0.003). These results suggest that patients with MDD may respond better to behavioral treatments such as CM than to desipramine plus buprenorphine. The ND cocaine-abusing, opiate-dependent patients may be more responsive to the anticraving effects of DMI.

Adult↗

PubMed1991

Pediatric cardiovascular effects of imipramine and desipramine.

Electrocardiograms were evaluated in 39 children and adolescents before and after the clinical use of imipramine and desipramine. The average increase in PR interval was 0.01 seconds. The PR interval increased by 0.02 seconds in 11 subjects, and a new first-degree atrioventricular block developed in two subjects. These changes were not related to the choice between imipramine and desipramine, the dose, or the method of administration. An increase in PR interval by 0.02 seconds or more did correlate with having an abnormality disclosed on a pretreatment electrocardiogram. The average increase in PR interval was 0.007 seconds for subjects with normal baseline electrocardiograms and 0.019 seconds for subjects with conduction and nonconduction abnormalities disclosed in baseline tracings. None of the electrocardiogram changes resulted in adverse clinical consequences.

Adolescent↗

PubMed1988

Alprazolam does not inhibit the metabolism of nortriptyline in depressed patients or inhibit the metabolism of desipramine in human liver microsomes.

In 10 patients treated with nortriptyline, the steady-state plasma concentrations of the parent drug and the active 10-hydroxy metabolite were very similar before and during concomitant treatment with alprazolam (0.5 mg orally t.i.d.). In human liver microsomes the 2-hydroxylation of desipramine was not inhibited by alprazolam. The absence of an inhibition by alprazolam on the hydroxylations of nortriptyline in vivo and of desipramine in vitro indicates that alprazolam is not metabolized by the debrisoquine hydroxylase.

Adult↗

PubMed1994

Decreased plasma concentrations of imipramine and desipramine following cholestyramine intake in depressed patients.

The effect of cholestyramine (4 g t.i.d. for 5 days) on the steady-state plasma concentrations of imipramine and desipramine was assessed in six depressed patients receiving chronic treatment with imipramine (75-150 mg/day). Compared with baseline, cholestyramine treatment was associated with an average 23% decrease in plasma imipramine levels [from 211 +/- 95 to 159 +/- 67 nmol/L, (mean +/- SD), p < 0.05], whereas desipramine levels decreased only marginally. These data suggest that administration of cholestyramine at therapeutic doses impairs the gastrointestinal absorption of concurrently prescribed imipramine by an extent that is potentially clinically significant.

Adult↗

PubMed1977

Influence of nomifensine and desipramine on tyramine pressor responses in healthy volunteers.

1. Pressor responses following a series of bolus intravenous injections of tyramine were used to assess the influence of single oral doses of nomifensine 75 mg on peripheral sympathetic neuronal uptake mechanisms in healthy volunteers. Desipramine 50 mg served as a positive control. 2. Following each treatment the effect of tyramine was diminished, with a shift to the right in the tyramine dose-response curve. In addition, there was a suggestion that in these experimental conditions nomifensine was less potent than desipramine.

Adult↗

PubMed1995

Effects of reboxetine and desipramine on the kinetics of the pupillary light reflex.

1. The aim of the study was to examine the effects of single doses of two antidepressants (desipramine and reboxetine) on three kinetic parameters (latency, amplitude, 75% recovery time) of the pupillary light reflex response. 2. Six healthy male volunteers participated in three experimental sessions at biweekly intervals. Each session was associated with one of three treatment conditions (placebo, desipramine 100 mg, reboxetine 4 mg). Subjects were allocated to sessions and treatments double-blind according to a Latin Square design. 3. Pupil diameter was measured in the dark with binocular television pupillometry. Reflex responses were evoked by 12 light stimuli (5.3 x 10(-5)-3.5 mW cm-2; 500 ms), and the kinetic parameters of each response were recorded. 4. The amplitude and 75% recovery time were positively, and latency was negatively correlated with the logarithm of light stimulus intensity. In the presence of the antidepressants the latency was prolonged, the amplitude was reduced and the 75% recovery time was shortened. There was a positive linear relationship between reflex amplitude and recovery time under all three treatment conditions; this relationship was not significantly affected by the antidepressants. 5. The effects of the antidepressants on latency and amplitude are consistent with the blockade of muscarinic cholinoceptors in the iris, whereas the shortening of the recovery time appears to be secondary to the reduction in amplitude.

Administration, Oral↗

PubMedDate not supplied

The effect of long-term chlorpromazine and desipramine treatment on adrenal corticosterone, cyclic AMP, and cholesterol distribution in rats.

1. Male rats were injected intraperitoneally with chlorpromazine (10 mg/kg) and desipramine (10 mg/kg), respectively, twice daily for 2 weeks. 2. The adrenal corticosterone concentrations were significantly lowered in chlorpromazine- and desipramine-treated rats. 3. Large dose of corticotrophin would increase the adrenal corticosterone level in chlorpromazine-treated but the adrenal response was significantly less than in the untreated controls. 4. The adrenal cyclic AMP level was similar in treated and control rats and the adrenal response to corticotrophin was not decreased at the cyclic AMP level. 5. The cholesteryl ester concentrations in the adrenals were significantly increased by drug treatment, although the free cholesterol concentrations were unchanged in the cytosol and mitochondrial cell fractions. 6. The possible site of action of chlorpromazine in suppressing corticosterone production is discussed.

Adrenal Glands↗