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PubMed1991

Differential effects of central and peripheral desipramine on sympathoadrenal function and heart rate in conscious rabbits.

The effects of the tricyclic antidepressant, desipramine, on the baroreflex regulation of renal sympathetic nerve activity (SNA) and heart rate (HR), the nasopharyngeal reflex, plasma epinephrine and blood pressure (BP) were studied in conscious rabbits. Renal SNA and HR were recorded during slow ramp changes in mean arterial pressure (MAP) and during inhalation of cigarette smoke. Intracisternal (i.c.) and intravenous (i.v.) drug administration were compared, using doses which produced similar total central nervous system (CNS) concentrations. After a brief sympathoexcitation, i.c. desipramine inhibited renal SNA and MAP and increased plasma adrenaline and HR. The renal sympathetic baroreflex was substantially attenuated, with reflex range and gain reduced by 46 and 31%, respectively, but the cardiac baroreflex and nasopharyngeal reflex were affected minimally. Sixty-four percent of the desipramine remaining in the brain was concentrated in the medulla oblongata and spinalis; levels in cortex, thalamus, midbrain, lower spinal cord, and peripheral tissues were minimal. Treatment with i.v. desipramine decreased renal SNA and increased HR without altering MAP or epinephrine release. There was a slight attenuation of the nasopharyngeal reflex, a slight baroreceptor-independent reduction in renal SNA at most MAP levels, and an augmentation of the cardiac baroreflex. The drug was uniformly distributed throughout the CNS; only 20% of the centrally accumulated dose was in the medulla. Thus, i.c. desipramine produces a differentiated pattern of sympathoadrenal effects, probably by increasing norepinephrine (NE) concentrations at several sites within the medulla. The effects of i.v. desipramine were different, owing to poorer access to the medulla and the consequences of peripheral neuronal uptake blockade, which may include a modest inhibition at the sympathetic ganglia and an excitation at cardiac and vasoconstrictor neuroeffector junctions.

Adrenal Glands↗

PubMed1997

Effect of the tricyclic antidepressant desipramine on protein kinase C in rat brain and rabbit platelets in vitro.

Protein kinase C (PKC), which participates in cellular responses to various stimuli such as hormones, neurotransmitters and growth factors, is essential for cell proliferation and differentiation. Desipramine, which is a tricyclic antidepressant, inhibited PKC activity in concentrations starting from 0.1 mmol/L in rat brain and its inhibitory effect on PKC activity did not involve competitive inhibition with calcium. However, rabbit platelets incubated with desipramine showed a biphasic dose-response change in PKC activity in vitro. The stimulatory effect of desipramine on PKC activity in rabbit platelets was observed over a concentration range of 0.5-2.0 mmol/L, and an inhibitory effect on PKC activity in platelets began to be seen at a concentration of 3.0 mmol/L desipramine. The stimulatory effects of desipramine and calcium on PKC activity in platelets appear to be occurring by the same mechanism. Several lines of evidence indicate that neurotransmitter uptake is linked to PKC activation. The present study supposes that the inhibitory effect of desipramine on neurotransmitter uptake may, at least in part, be associated with its inhibitory or stimulatory effect on PKC.

Animals↗

PubMed1975

Effects of desipramine on neuronal responses to dopamine, noradrenaline, 5-hydroxytryptamine and acetylcholine in the caudate nucleus of the rat.

1 The sensitivity of single neurones to microelectrophoretically applied dopamine, noradrenaline (NA), 5-hydroxytryptamine (5-HT) and acetylcholing (ACh) was investigated in the caudate nucleus of the rat, anaesthetized with halothane. Both excitatory and depressant responses could be observed to each of the agonists. There was a high correlation between the direction of responses to dopamine and noradrenaline, whereas there was no significant correlation between the direction of responses to dopamine and ACh. 2 The effect of desipramine was studied on both excitatory and depressant responses to dopamine, NA and 5-HT, and on excitatory responses to ACh. Both potentiation and antagonism of neuronal responses to monoamines and ACh could be observed after a brief application of desipramine. 3 Excitatory responses to glutamate were not affected by desipramine. 4 The observation that responses to dopamine and NA can be potentiated by desipramine in the caudate nucleus suggests that uptake blockade is not a prerequisite for potentiation. 5 It is suggested that the potentiation of neuronal responses to dopamine by desipramine may be responsible for the therapeutic efficacy of desipramine in Parkinson's disease.

Acetylcholine↗

PubMed1976

Potentiation by desipramine of neuronal responses to mescaline.

The effect of desipramine on responses of single cortical neurones to mescaline was studied by the microelectrophoretic technique. Both potentiation and antagonism of responses to mescaline by desipramine were observed. The antagonism may be related to the alpha-adrenolytic action of desipramine. The potentiation is unlikely to reflect the uptake blocking action of desipramine, since desipramine does not block the uptake of mescaline in the cerebral cortex. It is suggested that the potentiation may be due to a post-synaptic action of desipramine.

Animals↗

PubMed1980

Comparison of mianserin with desipramine, maprotiline and phentolamine on cardiac presynaptic and vascular postsynaptic alpha-adrenoceptors and noradrenaline reuptake in pithed normotensive rats.

1 The cardiovascular effects of intravenous desipramine (0.03 and 0.1 mg/kg), maprotiline (0.5 mg/kg), mianserin (1.0 and 3.0 mg/kg) and phentolamine (0.25 mg/kg) were examined and compared in pithed rats. Several experimental procedures were used in order to distinguish between the effects of the compounds on cardiac presynaptic alpha-adrenoceptors and on neuronal noradrenaline reuptake, as inhibition of either mechanism produces an increase of neurotransmitter concentration within the sympathetic synapse and therefore results in a greater end organ response.2 Pressor responses elicited by noradrenaline were potentiated by desipramine and maprotiline, reduced by phentolamine and not significantly modified by mianserin. However, all four compounds inhibited the pressor action of tyramine. Furthermore, mianserin reduced the pressor response to adrenaline.3 Desipramine, maprotiline and mianserin, but not phentolamine enhanced the positive chronotropic effects of noradrenaline, without affecting those of isoprenaline.4 All four compounds abolished the clonidine-induced inhibition of heart rate responses to short term electrical stimulation of the spinal cord. Moreover, in rats with a persistent tachycardia (induced by continuous stimulation of the thoracic spinal cord) desipramine, maprotiline and mianserin further increased heart rate. This effect was also observed in animals pretreated with phentolamine, administered in order to inhibit cardiac presynaptic alpha-adrenoceptors.5 In rats with a sustained tachycardia (100 beats/min produced by electrical stimulation of the spinal cord) both mianserin and phentolamine, in contrast to desipramine, shifted the clonidine heart rate dose-response curve to the right. Phentolamine was about 34 times more potent than mianserin in this respect.6 In pithed, reserpine-treated rats, the pressor responses to clonidine were not significantly modified by desipramine. The dose-response curves were shifted to the right by phentolamine (0.25 mg/kg) and mianserin (3.0 mg/kg).7 These results indicate that mianserin is an antagonist of both cardiac presynaptic and vascular postsynaptic alpha-adrenoceptors and also inhibits the neuronal reuptake of noradrenaline.

Animals↗

PubMed1982

A double-blind study of zimelidine, a serotonin uptake inhibitor, and desipramine, a noradrenaline uptake inhibitor, in endogenous depression. II. Biochemical findings.

In a comparative evaluation of zimelidine, a potent serotonin (5-HT) uptake inhibitor, and desipramine, a potent noradrenaline (NA) uptake inhibitor, 65 hospitalized patients with endogenous depression were evaluated for the following biochemical variables: 5-HT uptake in platelets, 5-HT concentration in whole blood, inhibition of the 5-HT and NA accumulation in rat hypothalamic synaptosomes incubated in the patients' plasma, the excretion of 4-hydroxy-3-methoxyphenyl glycol (HMPG) in urine and the pretreatment levels of the amine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and HMPG in cerebrospinal fluid (CSF). results of the biochemical studies confirmed that zimelidine and desipramine have different profiles with respect to monoamine uptake. Thus zimelidine caused more marked inhibition of 5-HT uptake than desipramine, especially in rat brain synaptosomes incubated in the patient's plasma. Desipramine plasma was much more effective than zimelidine plasma in inhibiting NA uptake in the same preparation. The urinary excretion of HMPG decreased significantly during desipramine treatment but remained unchanged during zimelidine treatment. The combined clinical and biochemical results indicated that patients with low pretreatment levels of 5-HIAA and HVA in CSF responded significantly better to zimelidine than patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of HMPG in CSF tended to respond better to desipramine than those with low levels of this NA metabolite.

Adult↗

PubMed1990

Effects of desipramine hydrochloride on peripheral sympathetic nerve activity.

Tricyclic antidepressants cause orthostatic hypotension and have antiarrhythmic effects that may be partially due to effects on the sympathetic nervous system. We studied the influence of intravenous desipramine hydrochloride on renal (n = 12) and lumbar (n = 5) nerve traffic and mean arterial pressure in alpha-chloralose-anesthetized rabbits with sinoaortic and vagal denervation. Desipramine administration resulted in dose-dependent inhibition of renal and lumbar nerve activity that was markedly reduced or abolished by yohimbine (0.5 mg/kg iv), an alpha 2-blocker that enters the brain rapidly. In contrast, administration of phentolamine (0.75 mg/kg iv), an alpha 1- and alpha 2-blocker with limited access to the brain, failed to alter the responses to desipramine. Because renal nerves are postganglionic and lumbar nerves are preganglionic, desipramine does not act via a ganglionic mechanism. Our results are best explained by an effect of desipramine on the sympathetic nervous system mediated via central alpha 2-receptors. This sympathoinhibitory effect of desipramine may contribute to its postural hypotensive effect and to its efficacy as an antiarrhythmic agent.

Adrenergic alpha-Antagonists↗

PubMed2000

Olfactory bulbectomy provokes a suppression of interleukin-1beta and tumour necrosis factor-alpha production in response to an in vivo challenge with lipopolysaccharide: effect of chronic desipramine treatment.

The olfactory bulbectomized (OB) rat has been developed as an animal model of depression and exhibits several behavioural and neurochemical characteristics that are qualitatively similar to those found in clinically depressed patients. In addition to the behavioural and neurochemical abnormalities seen in OB rats, it has been reported that these animals have alterations in a number ex vivo measures of immune function many of which are reversed following chronic antidepressant treatment. In the present study we sought to examine the effects of olfactory bulbectomy on responsiveness to an in vivo immune challenge with bacterial lipopolysaccharide (LPS; 100 microg/kg, i.p.). In addition, the effect of chronic treatment with the tricyclic antidepressant desipramine (7.5 mg/kg, i.p.) on bulbectomy related behavioural changes, hypothalamic-pituitary-adrenal axis activity and immune responsiveness was evaluated. To our knowledge this is the first time that in vivo immunological responsiveness has been examined in the OB rat model of depression. OB rats exhibited a characteristic hyperactive response in a novel 'open field' environment, which was attenuated following chronic desipramine treatment. LPS provoked a large increase in circulating interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in vehicle treated sham operated animals. Vehicle treated OB rats displayed a significant impairment in LPS-induced IL-1beta (54%) and TNF-alpha (70%) secretion compared to their sham operated controls, an effect that was potentiated following chronic desipramine treatment. Furthermore, sham animals that were chronically treated with desipramine displayed decreases in LPS-provoked IL-1beta (51%) and TNF-alpha (49%) secretion compared to vehicle treated counterparts. In addition, LPS-induced alterations in corticosterone and adrenal ascorbic acid concentrations were also attenuated by bulbectomy, an effect that was further enhanced following chronic desipramine treatment. In conclusion, these data provide evidence that olfactory bulbectomy in the rat impairs the ability of macrophages to produce the proinflammatory cytokines IL-1beta and TNF-alpha following an in vivo challenge with bacterial LPS. Whilst chronic treatment with desipramine normalized the behavioural hyperactivity observed in OB rats, such treatment further impaired LPS-induced IL-1beta and TNF-alpha secretion in bulbectomized rats.

Adrenal Cortex↗

PubMed1985

A comparison of the safety and efficacy of alprazolam and desipramine in moderately severe depression.

Fifty-four patients (34 outpatients, 20 inpatients) fulfilling Research Diagnostic Criteria for Definite Major Depressive Disorder were enrolled in a double-blind study comparing the antidepressant effects of alprazolam versus desipramine. The mean daily dose of alprazolam and desipramine at study termination was 3.78 mg and 208 mg respectively. As there were no significant demographic or clinical differences between outpatients and inpatients, both groups were combined in data analysis. Using the Hamilton Depression Rating Scale (HAM-D) both drug groups showed highly significant improvement beginning with the first week of active drug treatment. HAM-D scores continued to decrease through study termination (six weeks of active drug). There were no significant differences when comparing alprazolam and desipramine (outpatients, inpatients, or both groups combined) on any of the subjective or objective psychometrics used in this study. Clinically, only twelve of thirty-four outpatients (35.3%) were felt to be "markedly or moderately" improved, suggesting that neither the outpatient alprazolam nor desipramine patients did particularly well with drug treatment. In terms of drug safety there was no difference between the alprazolam and desipramine in the number of excessive or serious drug side effects. However, five of twenty-nine alprazolam patients had to discontinue therapy because of excessive drowsiness, and two of the alprazolam outpatients had motor vehicle accidents directly related to this adverse event. Alprazolam appeared as effective as desipramine in the pharmacotherapy of this group of depressed outpatient and inpatients. Alprazolam appeared well-tolerated by most subjects although drowsiness was a common--and at times serious--medication side effect.

Adult↗

PubMed1991

Comparison of amantadine and desipramine combined with psychotherapy for treatment of cocaine dependence.

We conducted a single-blind, random assignment, placebo-controlled, 12-week comparison of desipramine hydrochloride and amantadine hydrochloride as adjunctive treatments to counseling for cocaine dependence. Subjects were 54 outpatients who met DSM III-R criteria for active cocaine dependence and who completed a minimum of 2 weeks of treatment. Subjects treated with fixed doses of 200 mg/day desipramine (N = 17), 400 mg/day amantadine-placebo (N = 16), and placebo (N = 21) did not differ for lifetime cocaine use, lifetime histories of psychopathology, admission scores on psychometric assessments, and sociodemographics. All treatment groups demonstrated dramatic and persistent decreases in cocaine use, craving for cocaine, and psychiatric symptoms consequent to treatment. Although there was a trend for more dropouts by subjects taking desipramine, there were no significant differences among treatment groups regarding retention in treatment, craving for cocaine, and decreased cocaine use confirmed by urine toxicology. There was a trend for subjects treated with desipramine to maintain longer periods of cocaine abstinence. Mean plasma concentration of desipramine in a subsample of our subjects was less than that recommended for treatment of depression, thus the dosage of desipramine may have been subtherapeutic.

Adult↗

PubMed1991

Role of norfluoxetine in the inhibition of desipramine metabolism and in the inhibition of serotonin uptake after fluoxetine administration to rats.

Fluoxetine, a serotonin uptake inhibitor, is known to inhibit the metabolism of some drugs including desipramine, resulting in increased brain and blood levels of desipramine when the drugs are co-administered to rats. Norfluoxetine, the N-desmethyl metabolite of fluoxetine, was found to be less potent than fluoxetine in increasing brain and blood levels of desipramine in rats. Norfluoxetine was essentially equipotent to fluoxetine in decreasing brain concentrations of 5-hydroxyindoleacetic acid (5-HIAA) as a consequence of serotonin uptake inhibition. After the injection of fluoxetine into rats, brain levels of fluoxetine predominated over those of norfluoxetine at 1 hour, but at longer times (out to 24 hours), norfluoxetine levels were higher in brain (and in liver) than fluoxetine levels. Brain levels of 5-HIAA were decreased for at least 24 hours after fluoxetine injection, due apparently to the persistence of and inhibition of serotonin uptake by norfluoxetine. When desipramine was injected 16 hrs after fluoxetine injection, brain levels of desipramine were no longer elevated. The results suggest that norfluoxetine contributes in a major way to the inhibition of serotonin uptake after fluoxetine administration but contributes less, if at all, to the inhibition of desipramine metabolism.

Animals↗

PubMed1988

Quantitative autoradiography of central beta adrenoceptor subtypes: comparison of the effects of chronic treatment with desipramine or centrally administered l-isoproterenol.

This study compares the regulation of the subtypes of central beta adrenoceptors produced by treatment of rats with desipramine (10 mg/kg i.p. twice daily for 10 days) to that caused by central infusion of l-isoproterenol (5 micrograms/hr for 7 days). Beta adrenoceptors were measured by quantitative autoradiography of the binding of [125I]iodopindolol ([125I]IPIN) to coronal sections of rat brain as well as the binding of this radioligand to homogenates of certain areas of brain. Administration of desipramine caused significant reductions in the total specific binding of [125I]IPIN in many areas of the brain, including regions of the amygdala, cerebral cortex, hippocampus, hypothalamus and thalamus. This reduction in the total specific binding of [125I]IPIN was primarily the result of a reduction in its binding to beta-1 adrenoceptors in most brain regions. With the exception of the paraventricular nuclei of the thalamus, no desipramine-induced change in the binding of [125I]IPIN to beta-2 adrenoceptors was observed in any region of the brain. Treatment of rats with desipramine did not alter the binding of [125I]IPIN to the caudate putamen, globus pallidus or the cerebellum. Intracerebroventricular fusion of the nonselective beta adrenoceptor agonist, isoproterenol, reduced the maximum binding site density of the binding of [125I]IPIN to homogenates of cerebellum and hypothalamus, but not to homogenates of cerebral cortex. Autoradiography of the binding of [125I]IPIN to brain sections from rats treated with isoproterenol revealed reductions in many subcortical areas and the cerebellum. In contrast to the effects produced by treatment with desipramine, reductions in the binding of [125I]IPIN after infusions of isoproterenol were a result of a decrease in the binding of [125I]IPIN to beta-2 adrenoceptors in most brain regions. Infusion of isoproterenol reduced the binding of [125I]IPIN to beta-2 adrenoceptors in 10 areas of brain in which the binding of the ligand to beta-1 adrenoceptors was not affected significantly. Inasmuch as there is a selective regulation of beta-1 adrenoceptors by the norepinephrine uptake blocker, desipramine, it may be inferred that these receptors are under the influence of endogenous norepinephrine. By contrast, the density of central beta-2 adrenoceptors are regulated more easily by an exogenous beta adrenoceptor agonist, even one like isoproterenol which is a full agonist at both beta-1 and beta-2 adrenoceptors.

Animals↗

PubMed1983

Evidence for lysosomotropic action of desipramine in cultured human fibroblasts.

The uptake and release of [3H]desipramine, an antidepressant drug, was investigated in cultures of human fibroblasts during single and repeated doses added to the culture medium. The resulting kinetics and the pH dependence suggest that desipramine is a lysosomotropic drug which is taken up into the cells by virtue of its amphiphilic character and concentrated in the acidic contents of the lysosomes by ion trapping. Similar to the lysosomotropic agent, chloroquine, desipramine interferes with the lysosomal degradation of endogenous sulfated mucopolysaccharides in a dose-dependent manner. In contrast to short time exposure, long-term treatment with desipramine produces intracellular granulation, possibly by interfering with the recycling of plasma membrane vesicles. The appearance of granular inclusions and the accumulation of intracellular desipramine which is difficult to exchange indicate a gradual formation of complexes with membrane phospholipids resulting in a lysosomal storage of desipramine.

Cells, Cultured↗

PubMed1984

Use of desipramine in depressed inpatients.

Studies of desipramine in depressed inpatients are reviewed and indications for the use of the drug in clinical practice, as well as selection of patients for research, are discussed. The relationship between plasma desipramine concentrations and response is examined in melancholic and elderly patients, and in those with delusional depression. Major adverse reactions and subjective complaints during studies of desipramine treatment are reviewed. Few side effects were associated with elevated plasma desipramine levels. The clinical significance of 2-OH-desipramine levels was studied, but measurement of this metabolite did not enhance understanding of the drug's effects. A new technique for rapid dose adjustment is presented, for which desipramine appears to be particularly well suited.

Age Factors↗

PubMed1995

The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine.

OBJECTIVES: Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette's syndrome (TS), a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder (ADHD) behaviors in children with TS + ADHD. METHODS: A double-blind, placebo-controlled protocol was used in which each subject served as his or her own control and received, in a randomly assigned fashion, 6-week medication cycles with clonidine (0.05 mg four times daily), desipramine (25 mg four times daily), and placebo. RESULTS: Thirty-seven children with TS+ADHD between the ages 7 to 13 years and of normal intellect were recruited, and 34 (31 males, 3 females) completed the entire protocol. Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists (CBCL), continuous performance tests, and neuropsychologic tests of executive function. Several markers for ADHD were shown to improve significantly (P < .05) after treatment with desipramine (parent linear analogue rating, parent CBCL "hyperactivity" subscale, and teacher CBCL subscales "nervous/overactive," "anxious," and "unpopular"). Improvement with desipramine was always superior to that noted with clonidine. Clinical improvement did not correlate with drug blood levels. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not on the Hopkins Motor/Vocal Tic Severity Scale, the Tourette Syndrome Severity Scale, or the Yale Global Tic Severity Scale. Clonidine did not significantly alter tic severity on any measure. CONCLUSION: The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS.

Adolescent↗

PubMed2000

Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine.

Drugs thought to be selective inhibitors of either the uptake of serotonin (5-HT) or norepinephrine (NE) are known to be effective antidepressants. In general, a relative selectivity for NE vs. 5-HT uptake inhibition greater than 50-fold in vitro is thought to be sufficient to maintain such selectivity in vivo. To explore this issue, we carried out a study in which depressed patients were treated with either the selective serotonin reuptake inhibitor (SSRI) paroxetine or the selective norepinephrine reuptake inhibitor (SNRI) desipramine. Patients were treated with either drug or placebo for 6 wk. Drug levels in plasma and platelet 5-HT content were measured 12 times during the treatment period using HPLC procedures. Both drug treatments caused a significant reduction of platelet 5-HT content. Paroxetine reduced platelet 5-HT content to approx. 1% of pretreatment levels (n = 3). The inhibition of 5-HT uptake by paroxetine appeared to be immediate and complete. Desipramine reduced platelet 5-HT content to 38.7+/-6.2 % of pretreatment levels (n = 5) at a mean plasma level of 195 ng/ml. The percent reduction of platelet 5-HT content after 6 wk of drug treatment was proportional to the steady state plasma level of desipramine. The IC50 value of desipramine to reduce platelet 5-HT was 135 ng/ml. These results demonstrate that therapeutic concentrations of the SNRI desipramine as well as the SSRI paroxetine inhibited serotonin uptake in platelets of depressed patients. If such effects occur in the brain, desipramine might have some component of its therapeutic effects due to actions on the uptake of 5-HT.

Journal Article↗

PubMed1982

Alteration of norepinephrine metabolism with desipramine and zimelidine in depressed patients.

Twelve patients with a major affective disorder were treated during the depressed phase of their illness with desipramine hydrochloride and/or zimelidine hydrochloride, and urinary excretion rates of norepinephrine and its major metabolites were examined. During treatment with desipramine, daily urinary excretion of norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), and vanillylmandelic acid was reduced, but urinary normetanephrine excretion was not significantly changed. In all patients, the proportion of urinary norepinephrine metabolites represented by normetanephrine was increased during desipramine treatment. Independent of treatment outcome, desipramine seemed to decrease total formation and metabolism of norepinephrine, which was reflected in decreases in the excretion rate of the catecholamine and its metabolites. These results are consistent with known actions of desipramine on the disposition of norepinephrine and represent alterations in the rate of norepinephrine formation and metabolism, resulting from inhibition of norepinephrine reuptake. Zimelidine, a new antidepressant, which is a relatively specific serotonin-uptake inhibitor, significantly reduced only urinary MHPG excretion without appearing to alter "whole-body" norepinephrine turnover. This effect of zimelidine on norepinephrine metabolism was unexpected. Current and previous findings concerning clorgyline, a relatively specific monoamine oxidase A inhibitor, suggest that three pharmacologically distinct classes of antidepressants, norepinephrine and serotonin-reuptake and monoamine oxidase type A inhibitors, all reduce central norepinephrine turnover in depressed patients.

Antidepressive Agents↗

PubMed1992

Desipramine treatment of cocaine dependence in methadone-maintained patients.

We performed a double-blind, placebo-controlled, randomized 12-week trial of desipramine hydrochloride treatment of cocaine dependence among methadone-maintained patients. Fifty-nine patients completed the 12-week medication trial (36 received desipramine and 23 received placebo), and 94% were recontacted 1, 3, and 6 months after treatment. There were significantly more dropouts in the desipramine than in the placebo group. Baseline to 12-week comparisons of Addiction Severity Index interview data indicated that both groups showed improvements. At 12 weeks, the desipramine group showed significantly better psychiatric status than the placebo group but did not differ from the placebo group on any of 21 other outcome measures, including cocaine use. During the 12-week medication phase and at the 1-month follow-up evaluation, urine toxicology screenings showed no significant difference between groups, but the placebo group had significantly less cocaine use at both the 3- and 6-month follow-up points. We conclude that desipramine has few benefits with regard to control of cocaine use in this population.

Adult↗