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Cell Biology International Jun 2024Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic...
Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig-2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig-2 positive cells count in hippocampi of chronic stress-exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig-2 proteins. This work underscores the amelioration of the stress-induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.
PubMed: 38890788
DOI: 10.1002/cbin.12200 -
European Journal of Clinical... Sep 2023We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of...
Synergistic combination of carvedilol, amlodipine, amitriptyline, and antibiotics as an alternative treatment approach for the susceptible and multidrug-resistant A. baumannii infections via drug repurposing.
We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of Acinetobacter baumannii infections caused by susceptible and multidrug-resistant strains. A. baumannii is a multidrug-resistant Gram-negative bacteria causing nosocomial infections, especially in intensive care units. It has been identified in the WHO critical pathogen list and this emphasises urgent need for new treatment options. As the development of new therapeutics is expensive and time consuming, finding new uses of existing drugs via drug repositioning has been favoured. Antimicrobial susceptibility tests were conducted on all 13 drugs according to CLSI. Drugs with MIC values below 128 μg/mL and control antibiotics were further subjected to synergetic effect and bacterial time-kill analysis. Carvedilol-gentamicin (FICI 0.2813) and carvedilol-amlodipine (FICI 0.5625) were determined to have synergetic and additive effect, respectively, on the susceptible A. baumannii strain, and amlodipine-tetracycline (FICI 0.75) and amitriptyline-tetracycline (FICI 0.75) to have additive effect on the multidrug-resistant A. baumannii strain. Most remarkably, both amlodipine and amitriptyline reduced the MIC of multidrug-resistant, including some carbapenems, A. baumannii reference antibiotic tetracycline from 2 to 0.5 μg/mL, for 4-folds. All these results were further supported by bacterial time-kill assay and all combinations showed bactericidal activity, at certain hours, at 4XMIC. Combinations proposed in this study may provide treatment options for both susceptible and multidrug-resistant A. baumannii infections but requires further pharmacokinetics and pharmacodynamics analyses and in vivo re-evaluations using appropriate models.
Topics: Humans; Anti-Bacterial Agents; Drug Repositioning; Amitriptyline; Carvedilol; Amlodipine; Drug Synergism; Microbial Sensitivity Tests; Acinetobacter Infections; Drug Resistance, Multiple, Bacterial; Tetracyclines; Acinetobacter baumannii
PubMed: 37428238
DOI: 10.1007/s10096-023-04634-5 -
Mediterranean Journal of Rheumatology Jun 2022Erythromelalgia is a disabling syndrome of paroxysmal vasodilation affecting the feet, hands and face characterised by patient's cooling behaviour to achieve symptom...
Erythromelalgia is a disabling syndrome of paroxysmal vasodilation affecting the feet, hands and face characterised by patient's cooling behaviour to achieve symptom relief. It can be primary or secondary and although a rare disorder it has been described in children and adolescents. We describe the case of a 14-year-old female diagnosed with primary erythromelalgia successfully treated with aspirin, amitriptyline, and carbamazepine.
PubMed: 36128208
DOI: 10.31138/mjr.33.2.256 -
Neurochemistry International Nov 2021The current study was designed to evaluate the transient antinociceptive interaction between amitriptyline and paracetamol in the formalin test. In addition, considering...
The current study was designed to evaluate the transient antinociceptive interaction between amitriptyline and paracetamol in the formalin test. In addition, considering other long-term neuroprotective mechanisms of these drugs, we hypothesized that this combination might exert some synergistic effects on neuropathic pain linked with its possible ability to prevent Wallerian degeneration (WD). The effects of individual and fixed-ratio of 1:1 combinations of orally administered amitriptyline and paracetamol were assayed in the two phases of the formalin test and in the chronic constriction injury (CCI) model in rats. Isobolographic analysis was employed to characterize the synergism produced by the combinations. Amitriptyline, paracetamol, and fixed-ratio amitriptyline-paracetamol combinations produced dose-dependent antinociceptive effects mainly on the inflammatory tonic phase. Repeated doses of individual drugs and their combination decreased CCI-induced mechanical allodynia in a dose-dependent manner. ED (formalin) and ED (CCI) values were estimated for the individual drugs, and isobolograms were constructed. Theoretical ED values for the combination estimated from the isobolograms were 16.5 ± 3.9 mg/kg and 26.0 ± 7.2 mg/kg for the single and repeated doses in persistent and neuropathic pain models, respectively. These values were significantly higher than the actually observed ED values, which were 0.39 ± 0.1 mg/kg and 8.2 ± 0.8 mg/kg in each model, respectively, indicating a synergistic interaction. Remarkably, CCI-induced sciatic nerve WD-related histopathological changes were prevented by this combination compared to either drug administered alone.
Topics: Acetaminophen; Administration, Oral; Amitriptyline; Analgesics, Non-Narcotic; Animals; Dose-Response Relationship, Drug; Drug Synergism; Male; Neuralgia; Pain Measurement; Rats; Rats, Sprague-Dawley
PubMed: 34411687
DOI: 10.1016/j.neuint.2021.105160 -
MBio Jun 2020Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux is an encouraging strategy to restore the antibacterial...
Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux is an encouraging strategy to restore the antibacterial activity of antibiotics. Chlorpromazine and amitriptyline have been shown to behave as efflux inhibitors. However, their mode of action is poorly understood. Exposure of serovar Typhimurium and to chlorpromazine selected for mutations within genes encoding RamR and MarR, regulators of the multidrug tripartite efflux pump AcrAB-TolC. Further experiments with Typhimurium containing AcrB D408A (a nonfunctional efflux pump) and chlorpromazine or amitriptyline resulted in the reversion of the mutant allele to the wild type. Together, this suggests these drugs are AcrB efflux substrates. Subsequent docking studies with AcrB from Typhimurium and , followed by molecular dynamics simulations and free energy calculations showed that chlorpromazine and amitriptyline bind at the hydrophobic trap, a preferred binding site for substrates and inhibitors within the distal binding pocket of AcrB. Based on these simulations, we suggest that chlorpromazine and amitriptyline inhibit AcrB-mediated efflux by interfering with substrate binding. Our findings provide evidence that these drugs are substrates and inhibitors of AcrB, yielding molecular details of their mechanism of action and informing drug discovery of new efflux inhibitors. Efflux pumps of the resistance nodulation-cell division (RND) superfamily are major contributors to multidrug resistance for most of the Gram-negative ESKAPE (, , , , , and species) pathogens. The development of inhibitors of these pumps would be highly desirable; however, several issues have thus far hindered all efforts at designing new efflux inhibitory compounds devoid of adverse effects. An alternative route to design relies on the use of marketed drugs, for which side effects on human health have been already assessed. In this work, we provide experimental evidence that the antipsychotic drugs chlorpromazine and amitriptyline are inhibitors of the AcrB transporter, the engine of the major RND efflux pumps in and serovar Typhimurium. Furthermore, calculations have provided a molecular-level picture of the inhibition mechanism, allowing rationalization of experimental data and paving the way for similar studies with other classes of marketed compounds.
Topics: Amitriptyline; Anti-Bacterial Agents; Bacterial Proteins; Chlorpromazine; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Proteins; Membrane Transport Proteins; Microbial Sensitivity Tests; Molecular Docking Simulation; Multidrug Resistance-Associated Proteins; Mutation; Protein Binding; Salmonella enterica
PubMed: 32487753
DOI: 10.1128/mBio.00465-20 -
Cureus May 2024Hyperprolactinemia is an endocrinological disorder that might arise from various physiologic or pathologic conditions, as well as from pharmacologic sources. These...
Hyperprolactinemia is an endocrinological disorder that might arise from various physiologic or pathologic conditions, as well as from pharmacologic sources. These pharmacologic sources include antidepressants, antipsychotics, and dopamine receptor-blocking agents. Amitriptyline is classified as a tricyclic antidepressant. While it is FDA-approved primarily for the treatment of depression, amitriptyline also demonstrates efficacy in managing various other conditions, such as anxiety, post-traumatic stress disorder, insomnia, chronic and neuropathic pain, and migraine prevention. We present a case of a 10-year-old patient with a history of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and migraine headaches who was incidentally found to have elevated prolactin levels while taking amitriptyline for migraine prophylaxis. While risperidone, an antipsychotic that can be used for ASD management, is commonly known to induce hyperprolactinemia, the association between amitriptyline and elevated prolactin is less frequently described in the literature. This case underscores the necessity for healthcare providers across various specialties to be aware of amitriptyline-induced hyperprolactinemia.
PubMed: 38826982
DOI: 10.7759/cureus.59604 -
The Medical Letter on Drugs and... Aug 2019
Review
Topics: Adult; Anti-Anxiety Agents; Anxiety Disorders; Cognitive Behavioral Therapy; Female; Humans; Pregnancy; Selective Serotonin Reuptake Inhibitors
PubMed: 31386647
DOI: No ID Found -
The Journal of Mental Health Policy and... Mar 2024Consensus-guidelines for prescribing antidepressants recommend that clinicians should be vigilant to match antidepressants to patient's medical history but provide no... (Observational Study)
Observational Study
BACKGROUND
Consensus-guidelines for prescribing antidepressants recommend that clinicians should be vigilant to match antidepressants to patient's medical history but provide no specific advice on which antidepressant is best for a given medical history.
AIMS OF THE STUDY
For patients with major depression who are in psychotherapy, this study provides an empirically derived guideline for prescribing antidepressant medications that fit patients' medical history.
METHODS
This retrospective, observational, cohort study analyzed a large insurance database of 3,678,082 patients. Data was obtained from healthcare providers in the U.S. between January 1, 2001, and December 31, 2018. These patients had 10,221,145 episodes of antidepressant treatments. This study reports the remission rates for the 14 most commonly prescribed single antidepressants (amitriptyline, bupropion, citalopram, desvenlafaxine, doxepin, duloxetine, escitalopram, fluoxetine, mirtazapine, nortriptyline, paroxetine, sertraline, trazodone, and venlafaxine) and a category named "Other" (other antidepressants/combination of antidepressants). The study used robust LASSO regressions to identify factors that affected remission rate and clinicians' selection of antidepressants. The selection bias in observational data was removed through stratification. We organized the data into 16,770 subgroups, of at least 100 cases, using the combination of the largest factors that affected remission and selection bias. This paper reports on 2,467 subgroups of patients who had received psychotherapy.
RESULTS
We found large, and statistically significant, differences in remission rates within subgroups of patients. Remission rates for sertraline ranged from 4.5% to 77.86%, for fluoxetine from 2.86% to 77.78%, for venlafaxine from 5.07% to 76.44%, for bupropion from 0.5% to 64.63%, for desvenlafaxine from 1.59% to 75%, for duloxetine from 3.77% to 75%, for paroxetine from 6.48% to 68.79%, for escitalopram from 1.85% to 65%, and for citalopram from 4.67% to 76.23%. Clearly these medications are ideal for patients in some subgroups but not others. If patients are matched to the subgroups, clinicians can prescribe the medication that works best in the subgroup. Some medications (amitriptyline, doxepin, nortriptyline, and trazodone) always had remission rates below 11% and therefore were not suitable as single antidepressant therapy for any of the subgroups.
DISCUSSIONS
This study provides an opportunity for clinicians to identify an optimal antidepressant for their patients, before they engage in repeated trials of antidepressants.
IMPLICATIONS FOR HEALTH CARE PROVISION AND USE
To facilitate the matching of patients to the most effective antidepressants, this study provides access to a free, non-commercial, decision aid at http://MeAgainMeds.com.
IMPLICATIONS FOR HEALTH POLICIES
Policymakers should evaluate how study findings can be made available through fragmented electronic health records at point-of-care. Alternatively, policymakers can put in place an AI system that recommends antidepressants to patients online, at home, and encourages them to bring the recommendation to their clinicians at their next visit.
IMPLICATIONS FOR FURTHER RESEARCH
Future research could investigate (i) the effectiveness of our recommendations in changing clinical practice, (ii) increasing remission of depression symptoms, and (iii) reducing cost of care. These studies need to be prospective but pragmatic. It is unlikely random clinical trials can address the large number of factors that affect remission.
Topics: Humans; Citalopram; Fluoxetine; Paroxetine; Sertraline; Bupropion; Nortriptyline; Amitriptyline; Duloxetine Hydrochloride; Venlafaxine Hydrochloride; Desvenlafaxine Succinate; Escitalopram; Trazodone; Doxepin; Prospective Studies; Cohort Studies; Retrospective Studies; Antidepressive Agents; Psychotherapy
PubMed: 38634393
DOI: No ID Found -
Agri : Agri (Algoloji) Dernegi'nin... Oct 2023Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and...
OBJECTIVES
Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and neuropathic pain patients. PGB is often combined with anxiolytics and antidepressants. We aimed to investigate the antidepressant and anxiolytic effects of PGB and compare its effects with those of antidepressant and anxiolytic drugs and their combined use.
METHODS
Wistar Albino rats were used, and PGB (5, 10, 20, and 40 mg/kg), amitriptylin (AMT), fluoxetine (FLX), ketamine (KET), and diazepam (DZM), as well as combinations of PGB (20 mg/kg) with AMT, FLX, KET, and DZM, were administered. Elevated plus maze, forced swimming, and locomotor activity tests were performed.
RESULTS
In the elevated plus maze, PGB10, 20, 40, AMT, FLX, and DZM increased open arm time. The PGB20+FLX combination increased compared to PGB20. In forced swimming, PGB doses increased immobility time. AMT, FLX, DZM, and KET decreased compared to control and PGB doses. Other combinations of PGB20 reversed immobility time, except FLX. In locomotor activity, PGB20, AMT, KET, and DZM decreased distance.
CONCLUSION
PGB had a depressant effect in all doses and a dose-dependently anxiolytic effect. In combinations of PGB with AMT, KET, and DZM, it reversed their antidepressant effects. We assumed FLX could be preferred instead of AMT in patients using PGB. When PGB is used in combination, drug interactions should be considered. These results are also very remarkable in terms of pharmacoeconomics.
Topics: Rats; Humans; Animals; Anti-Anxiety Agents; Pregabalin; Rats, Wistar; Antidepressive Agents; Fluoxetine; Amitriptyline; Ketamine; Epilepsy
PubMed: 37886867
DOI: 10.14744/agri.2022.98474 -
Neurogastroenterology and Motility Jan 2022Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficult-to-treat... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Irritable bowel syndrome (IBS) is a highly prevalent and economically burdensome condition; and pain is often the most unpleasant, disruptive, and difficult-to-treat symptom. Visceral hypersensitivity is a common feature driving pain in IBS, suggesting that neuropathic mechanisms may be implicated. We conducted a systematic review of available evidence to examine the role of anti-neuropathic medicines in the management of pain in IBS.
METHODS
We systematically searched scientific repositories for trials investigating conventional oral, and/or parenteral, pharmaceutical antineuropathic treatments in patients with IBS. We summarized key participant characteristics, outcomes related to pain (primary outcome), and selected secondary outcomes.
KEY RESULTS
We included 13 studies (n = 629 participants): six investigated amitriptyline, three duloxetine, three pregabalin, and one gabapentin. There was considerable methodological and statistical heterogeneity, so we performed a narrative synthesis and limited meta-analysis. Amitriptyline was most extensively studied, though only in diarrhea-predominant patients. In individual trials, amitriptyline, pregabalin and gabapentin generally appeared beneficial for pain outcomes. While duloxetine studies tended to report improvements in pain, all were un-controlled trials with high risk of bias. Meta-analysis of three studies (n = 278) yielded a pooled relative-risk of 0.50 (95%CI 0.38-0.66) for not improving with anti-neuropathic agent vs control. We did not identify any eligible studies investigating the role of parenteral anti-neuropathics.
CONCLUSIONS AND INFERENCES
Anti-neuropathic analgesics may improve pain in IBS, and deserve further, high-quality investigation, potentially considering parenteral administration and agents with minimal gastrointestinal motility effects. Investigation of amitriptyline's efficacy in non-diarrhea-predominant subtypes is currently lacking, and we recommend particular caution for its use in IBS-C.
Topics: Abdominal Pain; Administration, Oral; Analgesics; Humans; Irritable Bowel Syndrome; Treatment Outcome
PubMed: 34755926
DOI: 10.1111/nmo.14289