Effects Of Nortriptyline Research Articles

Nortriptyline Modulates the Migration of Peripheral Blood Lymphocytes and Monocytes in Patients with Chronic Obstructive Pulmonary Disease.

In the present study, the effect of nortriptyline (1 and 10 μM), budesonide (10 nM) and their combination on the migration of peripheral blood lymphocytes and monocytes from patients with chronic obstructive pulmonary disease (COPD) towards chemokines CCL5 and CXCL10 was evaluated by flow cytometry. Nortriptyline (10 μM), both alone and in combination with budesonide, inhibited the migration of T helper cells, cytotoxic T lymphocytes, NK cells and B lymphocytes towards CCL5 and CXCL10, as well as enhanced monocyte migration towards these chemokines. The combination of nortriptyline (1 μM) and budesonide suppressed the chemotaxis of lymphocyte subpopulations towards CXCL10, but not towards CCL5, more effectively than budesonide alone. The combination of nortriptyline (10 μM) and budesonide inhibited the migration of lymphocyte subpopulations towards CCL5 and CXCL10 and activated monocyte chemotaxis towards both chemokines more effectively than budesonide alone. The results of this study demonstrate the ability of nortriptyline alone to modulate the migration of peripheral blood lymphocytes and monocytes from patients with COPD and to potentiate the effects of budesonide.

The Effects of Chemicals Used For Suicide on Insect Succession, Diversity and Development: An Animal Model

It has proven that the presence of different chemicals can affect the succession patterns of necrophagousinsects. A comprehensive study was designed on the effects of nortriptyline, diazinon, and aluminumphosphate on arthropod’s succession and diversity on cadavers.Sixteen rabbits in two groups were used as a model in this study, 12 of them were treated with the drugsand were placed in two habitats (sun and shade) based on the study design. For each group, one cagewas considered as control. Insects were collected twice a day from the cadavers and identified.In total, 549 necrophagous insects from five families, were collected from all the carcasses. Chrysomyaalbiceps was the dominant insect on all cadavers, expect for one treated with diazinon, in which it wasdisplaced by Dermestes frischii. The highest number of insects were collected on the sixth day for allcadavers. The majority were collected from the shaded cages.Generally, the species diversity was higher for all the cadavers treated with the drugs compared to thecontrol cadavers. The results showed that the presence of diazinon in the cadaver can repel necrophagousinsects, on the contrary nortriptyline seems to attract more species/specimen.

Nortriptyline enhances corticosteroid sensitivity of blood T cells from patients with chronic obstructive pulmonary disease.

Steroid unresponsiveness is a significant problem in the management of chronic obstructive pulmonary disease (COPD). The tricyclic antidepressant nortriptyline has been reported to reverse corticosteroid resistance induced by oxidative stress. This study examined the potential synergistic anti-inflammatory effects of nortriptyline and corticosteroids in T lymphocytes from patients with COPD and the molecular mechanisms underlying their action. Peripheral blood mononuclear cells (PBMCs) or whole blood cells from COPD patients were incubated with budesonide, nortriptyline, or their combinations and stimulated with phytohaemagglutinin (PHA) or phorbol myristate acetate (PMA) plus ionomycin. The release of interleukin 4 (IL-4), IL-5, IL-8 and other mediators from PBMCs was measured by ELISA. Intracellular pro-inflammatory cytokines, glucocorticoid receptor (GR) and its isoform GRβ, histone deacetylase 2 (HDAC2), phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and p65 nuclear factor-κ (p65 NF-κB) were determined in CD4+ and CD8+ T cells using flow cytometry. Nortriptyline 10 μM decreased PHA-induced release of cytokines: IL-4, IL-5, IL-13, IL-17A, IL-33, macrophage migration inhibitory factor and thymic stromal lymphopoietin (TSLP). This drug alone also reduced the percentage of IL-4, IL-8, interferon gamma (IFNγ) positive CD4+ T cells and IL-4, IL-8 expressing CD8+ T cells stimulated with PMA/ionomycin, whereas nortriptyline 1 μM had less pronounced effect. The combination of budesonide 10 nM with nortriptyline 10 μM was more potent at suppressing IL-4, IL-5, IL-8, IL-13, IL-17A, TSLP secretion from PBMCs, as well as IL-4, IL-8, IFNγ, GRβ expression by CD4+ and CD8+ T cells when compared with single budesonide treatment. The association of budesonide 10 nM and Nt (1 μM to 10 μM) effectively decreased p38 MAPK and p65 NF-κB phosphorylation and increased HDAC2 expression in both CD4+ and CD8+ T cells. In conclusion, nortriptyline alone demonstrates anti-inflammatory effects on blood T lymphocytes from COPD patients. Nortriptyline may also potentiate the effects of glucocorticoids and overcome corticosteroid insensitivity.

Exposure to tricyclic antidepressant nortriptyline affects early-life stages of zebrafish (Danio rerio)

Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006–500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.

Effect of Nortriptyline on Spreading Depolarization

Background: Spreading depolarization is associated with the extension of lesion size and complications in some important neurological diseases such as stroke, epilepsy, migraine, and traumatic brain injury. Objectives: This study aimed to reveal some molecular aspects of spreading depolarization and suggesting new therapeutic targets for its control by changing the function of different astrocytic and neuronal ion channels. Methods: The effects of nortriptyline on spreading depolarization in cortical and hippocampal tissues and on the electrophysiological properties of CA1 hippocampal pyramidal neurons were assessed by extra- and intracellular recording, following washing rat brain slices by the drug. Results: Nortriptyline made a significant increase in the amplitude of spreading depolarization in cortical and hippocampal tissues relative to control but did not change the duration significantly in each of the tissues. No significant difference was found in the effects of spreading depolarization on the electrophysiological properties of the CA1 pyramidal neurons between nortriptyline and control groups. Conclusions: The stimulating effect of nortriptyline on spreading depolarization is probably related to the augmentation of extracellular potassium collection in the cortex and hippocampus due to inhibition of astrocytic potassium scavenging function. This change can make more neurons prone to depolarization and increase the overall amplitude of spreading depolarization waves. Further studies should assess the effect of enhancing the clearance function of astrocyte-specific inwardly rectifying potassium channels, Kir4.1, or preventing other factors contributing to spreading depolarization on control of the process.

In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma.

Drug repurposing has been proved to be an effective strategy to meet the urgent need for novel anticancer agents for multiple myeloma (MM) treatment. In this work, we aimed to investigate the anticancer effect and mechanism of tricyclic antidepressant nortriptyline (NTP) on the U266 MM cell line. The in vitro inhibitory effect of NTP at various doses and time points was studied. The combination potential of cisplatin-NTP was also investigated. Cell cycle analysis and three flow cytometric apoptosis assays were performed. NTP showed dose- and time-dependent inhibitory effects on the U266 MM cell line. NTP had greater inhibitory effect than cisplatin (IC50 26 µM vs. 40 µM). The cisplatin-NTP combination is antagonistic. In addition to G2/M phase cell cycle arrest, NTP induced apoptosis as indicated by mitochondrial membrane potential and caspase-3 and annexin V assays. NTP has inhibitory and apoptotic effects on U266 MM cells. The cisplatin-NTP combination indicated strong antagonism, which may have significant clinical relevance since antidepressants are commonly employed in adjuvant therapy for cancer patients. Based on these findings, the therapeutic potential of NTP for MM treatment should be investigated with in-depth mechanistic studies and in vivo experiments.

P.1.g.104 Anxiolytic and antidepressant effects of nortriptyline in association with alpha-lipoic acid in the reserpine induced depression model

P.1.g.104 Anxiolytic and antidepressant effects of nortriptyline in association with alpha-lipoic acid in the reserpine induced depression model

Effect of Nortriptyline on Symptoms of Idiopathic Gastroparesis

Gastroparesis remains a challenging syndrome to manage, with few effective treatments and a lack of rigorously controlled trials. Tricyclic antidepressants are often used to treat refractory symptoms of nausea, vomiting, and abdominal pain. Evidence from well-designed studies for this use is lacking. To determine whether treatment with nortriptyline results in symptomatic improvement in patients with idiopathic gastroparesis. The NORIG (Nortriptyline for Idiopathic Gastroparesis) trial, a 15-week multicenter, parallel-group, placebo-controlled, double-masked, randomized clinical trial from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC), comparing nortriptyline with placebo for symptomatic relief in idiopathic gastroparesis. One hundred thirty patients with idiopathic gastroparesis were enrolled between March 2009 and June 2012 at 7 US academic medical centers. Patient follow-up was completed in October 2012. Inclusion criteria included delayed gastric emptying and moderate to severe symptom scores using the Gastroparesis Cardinal Symptom Index (GCSI). INTERVENTIONS Nortriptyline vs placebo. Study drug dose was increased at 3-week intervals (10, 25, 50, 75 mg) up to 75 mg at 12 weeks. The primary outcome measure of symptomatic improvement was a decrease from the patient's baseline GCSI score of at least 50% on 2 consecutive 3-week GCSI assessments during 15 weeks of treatment. The primary symptomatic improvement outcome did not differ between 65 patients randomized to nortriptyline vs 65 patients randomized to placebo: 15 (23% [95% CI, 14%-35%]) in the nortriptyline group vs 14 (21% [95% CI, 12%-34%]) in the placebo group (P = .86). Treatment was stopped more often in the nortriptyline group (19 [29% {95% CI, 19%-42%}]) than in the placebo group (6 [9%] {95% CI, 3%-19%}]) (P = .007), but numbers of adverse events were not different (27 [95% CI, 18-39] vs 28 [95% CI, 19-40]) (P = .89). Among patients with idiopathic gastroparesis, the use of nortriptyline compared with placebo for 15 weeks did not result in improvement in overall symptoms. These findings do not support the use of nortriptyline for idiopathic gastroparesis. clinicaltrials.gov Identifier: NCT00765895.

Influence of ABCB1 (P‐glycoprotein) haplotypes on nortriptyline pharmacokinetics and nortriptyline‐induced postural hypotension in healthy volunteers

A single nucleotide polymorphism in ABCB1, which encodes P-glycoprotein, has retrospectively been associated with symptoms of nortriptyline-induced postural hypotension in depressed patients. This finding needs to be replicated in independent studies before recommendations regarding pharmacogenetic testing can be made. In a prospective study of healthy volunteers homozygous for ABCB1 (1236-2677-3435, TTT/TTT or CGC/CGC), a single dose of nortriptyline was administered, plasma exposure was determined and blood pressure and heart rate were monitored during posture change. No differences between ABCB1 haplotype groups were found in plasma exposure of nortriptyline and its active metabolites, E- and Z-10-hydroxynortriptyline. The heart rate response to posture change was increased with nortriptyline, whereas there was no difference in blood pressure response. However, no differences between haplotype groups were observed except that the pre dose heart rate response to standing was greater in the TTT than CGC homozygotes. The association between ABCB1 polymorphisms and nortriptyline-induced postural hypotension found in a previous study could not be confirmed. The results raise the possibility of a predisposition in heart rate response in the TTT homozygotes rather than an effect of nortriptyline. AIMS To investigate the influence of ABCB1 (1236-2677-3435) polymorphisms on nortriptyline pharmacokinetics and nortriptyline-induced postural hypotension in healthy volunteers. Genetic screening of 67 healthy volunteers identified eight CGC homozygotes and nine TTT homozygotes of ABCB1 (1236-2677-3435), who were administered a single dose of nortriptyline 25 mg. Plasma exposure of nortriptyline and its active metabolites, E- and Z-10-hydroxynortriptyline, was determined over 72 h. Heart rate and blood pressure responses to posture change (active standing and passive head-up tilt) were measured continuously using finger plethysmography. There were no differences in plasma exposure between ABCB1 haplotype groups, as the geometric mean (95% CI) AUC(0,72 h) ratios were 0.98 (0.94, 1.03), 1.02 (0.96, 1.09) and 0.95 (0.80, 1.10) for nortriptyline, E- and Z-10-hydroxynortriptyline, respectively. The pre dose heart rate response to standing was greater in the TTT than CGC homozygotes (mean (95% CI) difference 7.4 (1.5, 13.4) beats min(-1) , P = 0.02). At t(max) at 8 h post dose, nortriptyline increased the heart rate response to posture change in all subjects with mean (95% CI) Δ heart rate values of 7.4 (3.6, 11.3) beats min(-1) on active standing (P = 0.0009) and 4.8 (2.0, 7.6) beats min(-1) on head-up tilt (P = 0.002), but no difference was observed between haplotype groups. There was no difference in blood pressure response to posture change in either group. The association between ABCB1 polymorphisms and nortriptyline-induced postural hypotension found in the previous study could not be confirmed. The results raise the possibility of a predisposition in heart rate response in the TTT homozygotes rather than an effect of nortriptyline.

Translating the smoking cessation properties of the antidepressant nortriptyline using reinforcing, discriminative and aversive stimulus effects of nicotine in rats

The antidepressant nortriptyline is a second-line pharmacotherapy for smoking cessation. Given that there is limited preclinical data available on the effects of nortriptyline on responses to nicotine, the present study sought to evaluate its effects on the reinforcing, discriminative stimulus (DS) and aversive effects of nicotine in male hooded Lister rats. The effects of nortriptyline (0, 1, 3 and 10 mg/kg, i.p.) on responding under the control of a second order schedule of nicotine (0.03 mg/kg per infusion) intravenous self-administration (IVSA; n = 7), food-maintained responding (n = 6), discrimination of nicotine (0.2 mg/kg, s.c.) from saline in a two-lever procedure controlled by a fixed ratio and variable interval schedule of food reinforcement (n = 12) and on the development of nicotine- and lithium-induced conditioned taste aversions (CTA) (n = 8 per dose of nortriptyline) were examined. Nortriptyline (3 mg/kg) reduced responding for nicotine in the drug-free interval in which behaviour was supported by nicotine-associated cues and subsequent intervals in which nicotine was available; however, food-maintained responding was also reduced at the same dose. Nortriptyline (3 mg/kg) blocked the development of a nicotine-induced CTA but not a lithium-induced CTA, indicating that these effects are unlikely to be due to non-specific effects of nortriptyline on taste perception or learning. Lastly, nortriptyline had no effect on the DS properties of nicotine. Nortriptyline appears to attenuate the reinforcing and aversive stimulus properties of nicotine, which may mediate its anti-smoking effects. However, the results should be interpreted with caution, as non-specific effects of nortriptyline may have contributed to these findings.

Inhibition of cytosolic phospholipase A2 is involved in the protective effect of nortriptyline on astrocytes exposed to combined oxygen-glucose deprivation

Inhibition of cytosolic phospholipase A2 is involved in the protective effect of nortriptyline on astrocytes exposed to combined oxygen-glucose deprivation

Effect of nortriptyline on cytosolic Ca2+ regulation and viability in PC3 human prostate cancer cells

AbstractThe effect of nortriptyline, a tricyclic antidepressant, on Ca2+ regulation and viability in human prostate cancer cells (PC3) is unclear. The present study examined whether nortriptyline altered basal [Ca2+]i levels in suspended PC3 cells using fura‐2 as a Ca2+‐sensitive fluorescent probe. Nortriptyline (50–500 µM) increased [Ca2+]i in a concentration‐dependent fashion. The Ca2+ signal was partially reduced by removing extracellular Ca2+, indicating that Ca2+ entry and release both contributed to the [Ca2+]i rise. Nortriptyline induced Mn2+ influx, leading to quench of fura‐2 fluorescence, suggesting Ca2+ influx. This Ca2+ influx was inhibited by activation of protein kinase C, but not by inhibition of L‐type Ca2+ channels. In Ca2+‐free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor, thapsigargin nearly abolished nortriptyline‐induced Ca2+ release. Conversely, pretreatment with nortriptyline greatly reduced the inhibitor‐induced [Ca2+]i rise, suggesting that nortriptyline released Ca2+ from the endoplasmic reticulum. Inhibition of phospholipase C did not change the nortriptyline‐induced [Ca2+]i rise. Nortriptyline at a concentration of 10 µM increased viability in a Ca2+‐independent manner. At 50 µM, nortriptyline killed 45% of cells. Nortriptyline at 10 µM did not induce apoptosis, but at 50 µM induced significant apoptosis measured by propidium iodide staining. Together, in PC3 cells, nortriptyline induced [Ca2+]i rises by causing the phospholipase C‐independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via the protein kinase C‐sensitive pathway. Nortriptyline also induced both cell proliferation and death in a concentration‐dependent manner. Apoptosis was involved in the cell death. Drug Dev Res 71:323–330, 2010. © 2010 Wiley‐Liss, Inc.

Effect of Nortriptyline on Ca(superscript 2+) Handling in SIRC Rabbit Corneal Epithelial Cells

To explore the effect of nortriptyline, a tricyclic antidepressant, on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) in corneal epithelial cells, [Ca²⁺]i levels in suspended SIRC rabbit corneal epithelial cells were measured by using fura-2 as a Ca²⁺-sensitive fluorescent dye. Nortriptyline at concentrations between 20-200 microM increased [Ca²⁺]i in a concentration-dependent manner. The Ca²⁺ signal was reduced partly by removing extracellular Ca²⁺. Nortriptyline-induced Ca²⁺ influx was inhibited by the store-operated Ca²⁺ channel blockers econazole and SK&F96365, the phospholipase A2 inhibitor aristolochic acid, and alteration of activity of protein kinase C. In Ca²⁺-free medium, 200 microM nortriptyline pretreatment greatly inhibited the rise of [Ca²⁺]i induced by the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ; another endoplasmic reticulum Ca²⁺ pump inhibitor) nearly abolished nortriptyline-induced [Ca²⁺]i rise. Inhibition of phospholipase C with U73122 decreased nortriptyline-induced [Ca²⁺]i rise by 75%. Taken together, nortriptyline induced [Ca²⁺]i rises in SIRC cells by causing phospholipase C-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ influx via store-operated Ca²⁺ channels.

Cytosolic phospholipase A2 inhibition is involved in the protective effect of nortriptyline in primary astrocyte cultures exposed to combined oxygen-glucose deprivation

Cytosolic phospholipase A2 inhibition is involved in the protective effect of nortriptyline in primary astrocyte cultures exposed to combined oxygen-glucose deprivation

β2‐adrenoceptors are critical for antidepressant treatment of neuropathic pain

Tricyclic antidepressants (TCAs) are one of the first-line pharmacological treatments against neuropathic pain. TCAs increase the extracellular concentrations of noradrenaline and serotonin by blocking the reuptake transporters of these amines. However, the precise downstream mechanism leading to the therapeutic action remains identified. In this work, we evaluated the role of adrenergic receptors (ARs) in the action of TCAs. We used pharmacological and genetic approaches in mice to study the role of ARs in the antiallodynic action of the TCA nortriptyline. Peripheral neuropathy was induced by the insertion of a polyethylene cuff around the main branch of the sciatic nerve. The specific role of beta(2)-AR was evaluated by studying beta(2)-AR(-/-) mice. We used von Frey filaments to assess mechanical allodynia. The antiallodynic action of nortriptyline was not affected by cotreatment with the alpha(2)-AR antagonist yohimbine, the beta(1)-AR antagonists atenolol or metoprolol, or the beta(3)-AR antagonist SR 59230A. On the contrary, the beta-AR antagonists propranolol or sotalol, the beta(1)/beta(2)-AR antagonists alprenolol or pindolol, or the specific beta(2)-AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in beta(2)-AR-deficient mice. Stimulation of beta(2)-AR is necessary for nortriptyline to exert its antiallodynic action against neuropathic pain. These findings provide new insight into the mechanism by which antidepressants alleviate neuropathic pain. Our results also raise the question of a potential incompatibility between beta-blockers that affect beta(2)-AR and antidepressant drugs in patients treated for neuropathic pain.

Nortriptyline Protects Mitochondria and Reduces Cerebral Ischemia/Hypoxia Injury

Nortriptyline, an antidepressant, was identified as a strong inhibitor of mitochondrial permeability transition by our screening of a library of 1040 drugs. Because mitochondrial permeability transition and consequent mitochondrial dysfunction have been implicated in acute neuronal death, we proposed to investigate the possible neuroprotective effects of nortriptyline in cerebral ischemia. The effects of nortriptyline were first studied in oxygen/glucose deprivation-induced death of primary cerebrocortical neurons, a cellular model of cerebral ischemia. Mitochondrial membrane potential, mitochondrial factor release, and caspase 3 activation were evaluated after its treatment. Nortriptyline was also studied in a mouse model, which was established by occlusion of the middle cerebral artery. The infarct volume, neurological function, and biochemical events were examined in the absence or the presence of nortriptyline. Nortriptyline inhibits oxygen/glucose deprivation-induced cell death, loss of mitochondrial membrane potential, downstream release of mitochondrial factors, and activation of caspase 3 in primary cerebrocortical neurons. Furthermore, it decreases infarct size and improves neurological scores after middle cerebral artery occlusion in mice. The ability of nortriptyline to inhibit mitochondrial factor release and caspase activation and further protect the animals correlates to its inhibitory effect on mitochondrial permeability transition in isolated mitochondria. This study indicated that nortriptyline is neuroprotective against cerebral ischemia. It also suggested mitochondrial permeability transition might be a valuable therapeutic target for acute neurodegeneration.

Effect of nortriptyline on intracellular Ca2+ handling and proliferation in human osteosarcoma cells.

The effect of the antidepressant nortriptyline, on bone cells is unknown. In human osteosarcoma MG63 cells, the effect of nortriptyline on intracellular Ca2+ concentration ([Ca2+]i) and proliferation was measured by using fura-2 and tetrazolium, respectively. Nortriptyline (> or = 10 microM) caused a [Ca2+]i rise in a concentration-dependent manner (EC50 = 200 microM). Nortriptyline-induced [Ca2+]i rise was prevented by 60% by removal of extracellular Ca2+ but was not altered by voltage-gated Ca2+ channel blockers. In Ca2+ -free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ -ATPase, caused a monophasic [Ca2+]i rise, after which the increasing effect of nortriptyline on [Ca2+]i was abolished; also, pretreatment with nortriptyline abolished thapsigargin-induced [Ca2+]i increase. U73122, an inhibitor of phospholipase C, did not affect nortriptyline-induced [Ca2+]i rise; however, activation of protein kinase C decrease nortriptyline-induced [Ca2+]i rise by 32%. Overnight incubation with 50 and 100 microM nortriptyline killed 78% and 97% of cells, respectively; while 10 microM nortriptyline had no effect. These data suggest that nortriptyline rapidly increases [Ca2+]i in human osteosarcoma cells by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release, and is cytotoxic at high concentrations.

Effect of nortriptyline and paroxetine on measures of chaos of heart rate time series in patients with panic disorder

Tricyclic antidepressants have notable cardiac side effects, and this issue has become important due to the recent reports of increased cardiovascular mortality in patients with depression and anxiety. Several previous studies indicate that serotonin reuptake inhibitors (SRIs) do not appear to have such adverse effects. Apart from the effects of these drugs on routine 12-lead ECG, the effects on beat-to-beat heart rate (HR) and QT interval time series provide more information on the side effects related to cardiac autonomic function. In this study, we evaluated the effects of two antidepressants, nortriptyline ( n=13), a tricyclic, and paroxetine ( n=16), an SRI inhibitor, on HR variability in patients with panic disorder, using a measure of chaos, the largest Lyapunov exponent (LLE) using pre- and posttreatment HR time series. Our results show that nortriptyline is associated with a decrease in LLE of high frequency (HF: 0.15–0.5 Hz) filtered series, which is most likely due to its anticholinergic effect, while paroxetine had no such effect. Paroxetine significantly decreased sympathovagal ratios as measured by a decrease in LLE of LF/HF. These results suggest that paroxetine appears to be safer in regards to cardiovascular effects compared to nortriptyline in this group of patients.

Effect of nortriptyline on the Day–Night systolic blood pressure difference in hypertensive and normotensive elderly depressed women

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Effect of nortriptyline and paroxetine on CYP2D6 activity

Effect of nortriptyline and paroxetine on CYP2D6 activity