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Archives of Disease in Childhood Dec 1971
Topics: Amitriptyline; Child; Enzymes; Female; Heart Failure; Humans; Imipramine; Poisoning
PubMed: 5129215
DOI: 10.1136/adc.46.250.887 -
Anesthesiology Jan 2005
Topics: Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Dose-Response Relationship, Drug; Injections; Neurotoxicity Syndromes; Pain Measurement; Rats; Sciatic Nerve
PubMed: 15618817
DOI: 10.1097/00000542-200501000-00043 -
Emergency Medicine Journal : EMJ Jan 2003A short cut review was carried out to establish whether gastric lavage is indicated after tricyclic antidepressant overdose. Altogether 82 papers were found using the... (Review)
Review
A short cut review was carried out to establish whether gastric lavage is indicated after tricyclic antidepressant overdose. Altogether 82 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.
Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Drug Overdose; Female; Gastric Lavage; Humans
PubMed: 12533375
DOI: 10.1136/emj.20.1.64 -
European Journal of Pharmacology Nov 2022Amitriptyline (AM) is a classical and typical tricyclic antidepressant drug. Despite its well-known effects on the nervous system, it has been described to work as a...
Dual effect of amitriptyline in the control of vascular tone: Direct blockade of calcium channel in smooth muscle cells and reduction of TLR4-dependent NO production in endothelial cells.
BACKGROUND AND PURPOSE
Amitriptyline (AM) is a classical and typical tricyclic antidepressant drug. Despite its well-known effects on the nervous system, it has been described to work as a TLR4 antagonist and several clinical works suggested some unexpected cardiovascular effects. The role of amitriptyline on vascular tone is not clear, thus we hypothesized that amitriptyline has a double effect on vascular tone by both endothelial TLR4-dependent nitric oxide down-regulation and calcium channel blockade in smooth muscle cells.
EXPERIMENTAL APPROACH
Changes in isometric tension were recorded on a wire myograph. NO production was evaluated by fluorescence microscopy and flow cytometry in the mouse aorta and EAhy926 cells using DAF fluorescence intensity. Calcium influx was evaluated in A7r5 cells by flow cytometry. Western blot was used to analyze eNOS and nNOS phosphorylation.
KEY RESULTS
AM reduced PE-induced contraction by calcium influx diminution in smooth muscle cells (F/F = 225.6 ± 15.9 and 118.6 ± 17.6 to CT and AM, respectively). AM impaired Ach-dependent vasodilation (Emax = 95.8 ± 1.4; 78.1 ± 1.8; 60.4 ± 2.9 and -7.4 ± 1.0 for CT, 0.01, 0,1 and 1 μmol/L AM, respectively) through reduction of calcium influx and NO availability and TLR4 antagonism in a concentration-dependent manner. AM or TLR4 gene deletion significantly reduced NO production (Fluorescence = 9503 ± 871.7, 2561 ± 282, 4771 ± 728 and 1029 ± 103 to CT, AM, TLR4 and AM + TLR4, respectively) by an increase in nNOS and reduction in eNOS phosphorylation in endothelial cells.
CONCLUSIONS AND IMPLICATIONS
Our data show that amitriptyline impaired vascular function through two different mechanisms: blockade of TLR4 in endothelial cells and consequent decrease in NO production and calcium influx reduction in smooth muscle and endothelial cells. We also suggest, for the first time, nNOS activity reduction by AM in non-neuronal cells.
Topics: Mice; Animals; Endothelial Cells; Calcium Channels; Amitriptyline; Toll-Like Receptor 4; Nitric Oxide; Endothelium, Vascular; Calcium; Antidepressive Agents, Tricyclic; Mice, Inbred C57BL; Vasodilation; Myocytes, Smooth Muscle
PubMed: 36088982
DOI: 10.1016/j.ejphar.2022.175255 -
Acta Poloniae Pharmaceutica 2013The aim of the present study was to assess the impact of combined therapy with rosuvastatin (10 mg/kg) and amitriptyline (10 mg/kg) on oxidation-reduction status in the...
The aim of the present study was to assess the impact of combined therapy with rosuvastatin (10 mg/kg) and amitriptyline (10 mg/kg) on oxidation-reduction status in the blood of rats. After 2-week application of drugs alone or their combination, the activity of glutathione peroxidase (GPX), glutathione reductase (GR) and total antioxidant status (TAS) were determined. It was noticed that combined therapy with rosuvastatin and amitriptyline significantly increased the activity of GPX in comparison to the group receiving only rosuvastatin and decreased the activity of GR in comparison to groups receiving only rosuvastatin or amitriptyline. However, the activity of these enzymes as a result of combined therapy was placed in the level of the control groups. Our studies indicated that the combined therapy with both drugs caused an increase of TAS compared to the groups of animals receiving only one of these drugs. The results indicate on the oxidation-reduction balance and increasing the antioxidant status in rats treated with rosuvastatin and amitriptyline.
Topics: Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Fluorobenzenes; Glutathione Peroxidase; Glutathione Reductase; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Injections, Intraperitoneal; Male; Oxidation-Reduction; Oxidative Stress; Pyrimidines; Rats; Rats, Wistar; Rosuvastatin Calcium; Sulfonamides
PubMed: 24147371
DOI: No ID Found -
PloS One 2020Herein, the interaction among the antidepressant drug amitriptyline hydrochloride (AMT) and a green gemini surfactant, ethane-1, 2-diyl...
Herein, the interaction among the antidepressant drug amitriptyline hydrochloride (AMT) and a green gemini surfactant, ethane-1, 2-diyl bis(N,N-dimethyl-N-tetradecylammoniumacetoxy) dichloride (14-E2-14), via numerous techniques such as tensiometry, fluorimetry, FT-IR and UV-visible spectroscopy in three different media (aqueous 0.050 mol·kg-1 NaCl, 0.50 and 1.0 mol·kg-1 urea) were investigated. AMT is used to treat mental illness or mood problems, such as depression. The aggregation of biologically active ingredients can enhance the bioavailability of hydrophobic drugs. A significant interaction between AMT and 14-E2-14 was detected by tensiometric study as the critical micelle concentration (cmc) of AMT+14-E2-14 is reduced upon an increase of mole fraction (α1) of 14-E2-14. The decrease in cmc indicates the nonideality of studied mixtures of different compositions. Although, employed drug AMT is freely soluble in the aqueous and non-aqueous system but is not hydrophobic enough to act as its carrier. Instead, gemini surfactant formed spherical micelles in an aqueous system and their high solubilization capability, as well as their relatively lower cmc value, makes them highly stable in vivo. The cmc values of AMT+14-E-14 mixtures in all cases were further decreased and increased in NaCl and urea solutions respectively as compared with the aqueous system. Numerous micellar, interfacial, and thermodynamic parameters have been measured by applying various theoretical models. The obtained changes in the physicochemical assets of AMT upon adding of 14-E2-14 are likely to enhance the industrial and pharmaceutical applications of gemini surfactants. The negative interaction parameters (βm and βσ), indicate synergistic attraction is occurring in the mixed systems. The aggregation number (Nagg), Stern-Volmer constant (Ksv), etc. are attained through the fluorescence method, also supporting the attractive interaction behavior of AMT+14-E2-14 mixtures in all solvents. The Nagg was found to increase in the salt solution and decrease in the urea system compared with the aqueous solution. FT-IR and UV-visible analysis also depict the interaction between the constituent alike tensiometry and fluorimetry methods. The results suggested that gemini surfactants may serve as a capable drug delivery agent for antidepressants, improving their bioavailability.
Topics: Amitriptyline; Cations; Esters; Micelles; Molecular Conformation; Solutions; Solvents; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Surface Tension; Surface-Active Agents; Thermodynamics
PubMed: 33156844
DOI: 10.1371/journal.pone.0241300 -
British Journal of Clinical Pharmacology 19771. The study consists of a double-blind evaluation of nomifensine and amitriptyline in a group of 37 patients with primary depressive illness. 2. The patients were... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1. The study consists of a double-blind evaluation of nomifensine and amitriptyline in a group of 37 patients with primary depressive illness. 2. The patients were referred by their family doctors on the basis that they would ordinarily have been prescribed a tricyclic antidepressant drug. Random allocation to the treatment groups took place. Assessment took place at weekly intervals over a 4-week period using the Visual Analogue Scale for depression and anxiety, and a side-effects check-list. Patients were also assessed on the Hamilton Depression Scale before the onset and at the end of the trial. 3. No significant difference was found between the two groups as regards relief from depression and anxiety, although marginal differences were found in favour of the amitriptyline group. 4. The overall frequency of side-effects was similar in the nomifensine and amitriptyline patients, But the development of severe side-effects was significantly more common in the amitriptyline group.
Topics: Adjustment Disorders; Adult; Affective Disorders, Psychotic; Amitriptyline; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Isoquinolines; Male; Middle Aged; Nomifensine; Psychotic Disorders
PubMed: 334229
DOI: 10.1111/j.1365-2125.1977.tb05758.x -
The Cochrane Database of Systematic... Jul 2011Abdominal pain-related functional gastrointestinal disorders (FGIDs) are among the most common medical problems in paediatric medicine. Frequently, physicians prescribe... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Abdominal pain-related functional gastrointestinal disorders (FGIDs) are among the most common medical problems in paediatric medicine. Frequently, physicians prescribe antidepressants as a second-line treatment for children and adolescents with FGIDs. To date, the evidence on the benefits and harms of antidepressants for the treatment of abdominal pain-related FGIDs has not been assessed systematically.
OBJECTIVES
The primary objectives were to conduct a systematic review to evaluate the efficacy and safety of antidepressants for the treatment of abdominal pain-related FGIDs in children and adolescents.
SEARCH STRATEGY
We searched The Cochrane Library, PubMed, EMBASE, IPA, CINAHL, PsycINFO, ISI Web of Science, Biosis Previews and the International Clinical Trials Registry Platform of the World Health Organization with appropriate filters (from inception to January 31, 2011).
SELECTION CRITERIA
For efficacy we included double-blind, randomised controlled trials (RCTs) of antidepressants for treatment of abdominal pain-related FGIDs in children and adolescents 18 years or younger. Open-label and uncontrolled experimental studies, as well as observational studies were eligible for the assessment of harms. The minimum study duration was 4 weeks. The minimum study size was 30 participants.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed all abstracts and full text articles, and rated the risk of bias for included studies. Data were extracted independently by one author and checked for accuracy by another author. Data were analysed using RevMan 5.
MAIN RESULTS
Two RCTs (123 participants), both using amitriptyline, met the pre-specified inclusion criteria. These studies provided mixed findings on the efficacy of amitriptyline for the treatment of abdominal pain-related FGIDs. The larger, publicly-funded study reported no statistically significant difference in efficacy between amitriptyline and placebo in 90 children and adolescents with FGIDs after 4 weeks of treatment. On intention-to-treat (ITT)- analysis, 59% of the children reported feeling better in the amitriptyline group compared with 53% in the placebo group (RR 1.12; 95% CI: 0.77 to 1.63; P = 0.54). The risk of bias for this study was rated as low.The second RCT enrolled 33 adolescents with irritable bowel syndrome. Patients receiving amitriptyline experienced greater improvements in the primary outcome, overall quality of life, at weeks 6, 10, and 13 compared with those on placebo (P= 0.019, 0.004, and 0.013, respectively). No effect estimates were calculated for the quality of life outcome because mean quality of life scores and standard deviations were not reported. For most secondary outcomes no statistically significant differences between amitriptyline and placebo could be detected. The risk of bias for this study was rated as unclear for most items. However, it was rated as high for other bias due to multiple testing. The results of this study should be interpreted with caution due to the small number of patients and multiple testing.The larger study reported mild adverse events including fatigue, rash and headache and dizziness. On ITT analysis, 4% of the amitriptyline group experienced at least one adverse event compared to 2% of the placebo group. There was no statistically significant difference in the proportion of patients who experienced at least one adverse event (RR 1.91; 95% CI 0.18 to 20.35; P = 0.59). The smaller study reported no adverse events. The methods of adverse effects assessment was poorly reported in both studies and no clear conclusions on the risks of harms of amitriptyline can be drawn.
AUTHORS' CONCLUSIONS
Clinicians must be aware that for the majority of antidepressant medications no evidence exists that supports their use for the treatment of abdominal pain-related FGIDs in children and adolescents. The existing randomised controlled evidence is limited to studies on amitriptyline and revealed no statistically significant differences between amitriptyline and placebo for most efficacy outcomes. Amitriptyline does not appear to provide any benefit for the treatment of FGIDs in children and adolescents. Studies in children with depressive disorders have shown that antidepressants can lead to substantial, sometimes life-threatening adverse effects. Until better evidence evolves, clinicians should weigh the potential benefits of antidepressant treatment against known risks of antidepressants in paediatric patients.
Topics: Abdominal Pain; Adolescent; Amitriptyline; Antidepressive Agents, Tricyclic; Child; Gastrointestinal Diseases; Humans; Irritable Bowel Syndrome; Randomized Controlled Trials as Topic
PubMed: 21735420
DOI: 10.1002/14651858.CD008013.pub2 -
Pain Dec 2021Tricyclic antidepressants that inhibit serotonin and noradrenaline reuptake, such as amitriptyline, are among the first-line treatments for neuropathic pain, which is...
Tricyclic antidepressants that inhibit serotonin and noradrenaline reuptake, such as amitriptyline, are among the first-line treatments for neuropathic pain, which is caused by a lesion or disease affecting the somatosensory nervous system. These treatments are, however, partially efficient to alleviate neuropathic pain symptoms, and better treatments are still highly required. Interactions between neurons and glial cells participate in neuropathic pain processes, and importantly, connexins-transmembrane proteins involved in cell-cell communication-contribute to these interactions. In a neuropathic pain model in rats, mefloquine, a connexin inhibitor, has been shown to potentiate the antihyperalgesic effect of amitriptyline, a widely used antidepressant. In this study, we further investigated this improvement of amitriptyline action by mefloquine, using the cuff model of neuropathic pain in mice. We first observed that oral mefloquine co-treatment prolonged the effect of amitriptyline on mechanical hypersensitivity by 12 hours after administration. In addition, we showed that this potentiation was not due to pharmacokinetic interactions between the 2 drugs. Besides, lesional and pharmacological approaches showed that the prolonged effect was induced through noradrenergic descending pathways and the recruitment of α2 adrenoceptors. Another connexin blocker, carbenoxolone, also improved amitriptyline action. Additional in vitro studies suggested that mefloquine may also directly act on serotonin transporters and on adenosine A1 and A2A receptors, but drugs acting on these other targets failed to amplify amitriptyline action. Together, our data indicate that pharmacological blockade of connexins potentiates the therapeutic effect of amitriptyline in neuropathic pain.
Topics: Amitriptyline; Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic; Mefloquine; Mice; Neuralgia; Rats
PubMed: 33769363
DOI: 10.1097/j.pain.0000000000002276 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2008Amitriptyline is a tricyclic antidepressant, considered the treatment of choice for different types of chronic pain, including chronic myofascial pain. Its... (Review)
Review
Amitriptyline is a tricyclic antidepressant, considered the treatment of choice for different types of chronic pain, including chronic myofascial pain. Its antinociceptive property is independent of its antidepressant effect. Although its analgesic mechanism is not precisely known, it is believed that the serotonin reuptake inhibition in the central nervous system plays a fundamental role in pain control. Although this medication is widely used in the prevention of chronic tension-type headache, few studies have investigated the efficacy of this treatment and the published results are contradictory. The objective of this article was to review the literature published on the use of amitriptyline in the prophylactic treatment of chronic tension-type headache, considering the level of scientific evidence of the different studies using the SORT criteria. From this review, 5 articles of evidence level 1, and another 5 articles of evidence level 2 were selected. Following analysis of the 10 studies, and in function of their scientific quality, a level A recommendation was made in favor of using amitriptyline in the treatment of chronic tension-type headache.
Topics: Amitriptyline; Analgesics, Non-Narcotic; Chronic Disease; Humans; Tension-Type Headache
PubMed: 18758401
DOI: No ID Found