Amitriptyline Research Articles

Amitriptyline nanoparticle repositioning prolongs the anti-allodynic effect of enhanced microglia targeting.

Aim: Amitriptyline (AMI) has been used to treat neuropathic pain. However, the clinical outcomes remain unsatisfactory, presumably due to a limited understanding of the underlying molecular mechanisms. Here, we investigated a drug repositioning strategy using a low-dose of AMI encapsulated in poly (D, L lactic-co-glycolic acid) (PLGA) nanoparticles (AMI NPs) for neuropathic pain, since PLGA nanoparticles are known to enhance delivery to microglia.Methods: We evaluated the anti-allodynic effects of AMI and AMI NPs on neuropathic pain by assessing behaviors and inflammatory responses in a rat model of spinal nerve ligation (SNL). While the anti-allodynic effect of AMI (30μg) drug injection on SNL-induced neuropathic pain persisted for 12h, AMI NPs significantly alleviated mechanical allodynia for 3days.Results: Histological and cytokine analyses showed AMI NPs facilitated the reduction of microglial activation and pro-inflammatory mediators in the spinal dorsal horn. This study suggests that AMI NPs can provide a sustained anti-allodynic effect by enhancing the targeting of microglia and regulating the release of pro-inflammatory cytokines from activated microglia.Conclusion: Our findings suggest that the use of microglial-targeted NPs continuously releasing AMI (2μg) as a drug repositioning strategy offers long-term anti-allodynic effects.

Empagliflozin significantly prevents QTc prolongation due to amitriptyline intoxication.

Empagliflozin (EMPA) is a sodium-glucose transporter-2 inhibitor used in the treatment of type 2 diabetes and has positive effects on cardiovascular outcomes. Amitriptyline (AMT) can be used in many clinical indications but leads to cardiotoxicity by causing QT prolongation. Our aim in this study was to determine how the effects of the concomitant use of empagliflozin and amitriptyline, which have been shown to have effects on sodium and calcium metabolism in cardiomyocytes, would cause an effect on QT and QTc intervals in clinical practice. Twenty-four male Wistar albino rats were randomised into four groups. The control group received only physiological serum (1 ml) via orogastric gavage (OG). The EMPA group received empagliflozin (10 mg/kg) via OG. The AMT group received amitriptyline (100 mg/kg) via OG. The AMT + EMPA group (n = 6) received amitriptyline (100 mg/kg) and empagliflozin (10 mg/kg). Under anaesthesia, QT and QTc intervals were measured at baseline, and in the first and second hours. In the AMT group, QT intervals and QTc values were found to be statistically longer than in the control group (p ≤ 0.001). Empagliflozin significantly ameliorated amitriptyline-induced QT and QTc prolongation. In the AMT + EMPA group, QT and QTc intervals were significantly lower compared to that in the AMT group (p < 0.01). In this study, we determined that empagliflozin significantly ameliorated amitriptyline-induced QT and QTc prolongation. This effect was probably due to the opposite effects of these two agents in the intracellular calcium balance. With more clinical trials, the routine use of empagliflozin may be suggested to prevent QT and QTc prolongation in diabetic patients receiving amitriptyline.

Analysis of the anti-Candida activity of tricyclic antidepressants in association with amphotericin B and their antifungal mechanisms.

Candida species are among the priority pathogens in the area of research and development. Due to the problems associated with resistance to antifungals, new therapeutic alternatives are necessary. In this regard, drug repositioning has gained prominence. The objective of this study was to evaluate the activity of three tricyclic antidepressants (TCAs) - amitriptyline (AMT), nortriptyline (NOR) and clomipramine (CLO) - isolated or associated with antifungals against strains of Candida spp., as well as to analyze the possible mechanism of action. Among the methods used were broth microdilution tests, tolerance level assessment, checkerboard assays, flow cytometry and fluorescence microscopy. Furthermore, Candida cells were visualized after treatments by scanning electron microscopy (SEM). AMT presented MIC 50% in the range of 16 to 128µg/mL, NOR from 8 to 128µg/mL, and CLO from 8 to 64µg/mL, with all three TCAs having a fungicidal inhibitory action profile. For these TCAs, there was synergism with amphotericin B (AMB) in 100% of the isolates. In association with fluconazole (FLC) and itraconazole (ITR), there were mostly indifferent interactions. TCAs isolated and associated with AMB reduced cell viability, promoted DNA fragmentation and damage, caused mitochondrial depolarization, externalization of phosphatidylserine, produced reactive oxygen species (ROS), decreased reduced glutathione (GSH) and increased carbonyl protein levels, causing morphological changes. The results suggest the antifungal mechanism of the TCAs works via the apoptotic pathway.

Amitriptyline and duloxetine attenuate activities of superficial dorsal horn neurons in a rat reserpine-induced fibromyalgia model

Fibromyalgia (FM) is an intractable disease with a chief complaint of chronic widespread pain. Amitriptyline (AMI) and duloxetine (DLX), which are antidepressant drugs, have been reported to ameliorate pain in patients with FM and pain-related behaviors in several rodent models of FM. However, the mechanisms of action of AMI and DLX are not yet fully understood. Here, we examined the effects of these drugs on the responsiveness of superficial dorsal horn (SDH) neurons in the spinal cord, using a rat FM model developed by injecting a biogenic amine depleter (reserpine). Extracellular recordings of SDH neurons in vivo demonstrated that bath application of AMI and DLX at concentrations of 0.1–1.0 mM on the dorsal surface of the spinal cord markedly suppressed spontaneous discharge and von Frey filament-evoked mechanical firing in SDH neurons. The suppression induced by the drugs was noted in a concentration-dependent manner and the suppressive effects resolved after washing the spinal cord surface. These results show that SDH neurons are the site of action for AMI and DLX in a rat reserpine-induced FM model. Spinal mechanisms may underlie the therapeutic effects of these drugs in patients with FM.

Adsorption of amitriptyline from aqueous solutions using magnetic graphene-based material: Isotherm, kinetics, and thermodynamic study

Amitriptyline (AMT) is an antidepressant often found in water environments. Due to its toxicity, in this work, AMT adsorption was proposed using graphene oxide (GO) and magnetic GO (GO·Fe3O4 1:1). The adsorbent characterizations were accomplished by FTIR, SEM, EDS, Raman spectroscopy, XRD, and VSM revealed the typical characteristics of the pristine GO and GO·Fe3O4 1:1. In the batch adsorption study, GO·Fe3O4 1:1 showed the highest adsorption capacity (91.84 mg g−1) and removal percentage (92 %) (at pH = 9.0, C0 = 50.0 mg L−1, adsorbent dosage = 0.5 g L−1, the temperature at 293 ± 1.00 K). Moreover, the Sips model showed the best adjustment for isothermal experimental data. This model suggests that the adsorption occurs at heterogeneous surfaces when the qs value increases with the increase in temperature (from 235.57 mg g−1 at 20 ºC to 463.34 mg g−1 at 50 ºC). The thermodynamic study confirms that AMT adsorption onto GO·Fe3O4 1:1 is a spontaneous and endothermic process (ΔH = 32.75 kJ mol−1). Elovich kinetic model presented the best adjustment for experimental data and showed that the adsorption rate (α) and surface coverage constant (β), decrease with the increase of the adsorbate dosage. Additionally, the ionic strength study reveals that a high concentration of NaCl (1.0 M) decreases the qe to 25.74 mg g−1. Lastly, after five consecutive adsorption/desorption cycles, the removal percentage of GO·Fe3O4 1:1 remained elevated (79 %). Overall, this paper reports the efficiency of GO·Fe3O4 1:1 on AMT removal, in addition to investigating the several variables involved in this adsorption.

Environmentally relevant concentrations of the tricyclic antidepressant, amitriptyline, affect feeding and reproduction in a freshwater mollusc

Antidepressant drugs (ADDs) are one of the most extensively used pharmaceuticals globally. They act at particularly low therapeutic concentrations to modulate monoamine neurotransmission, which is one of the most evolutionary conserved pathways in both humans and animal species including invertebrates. As ADDs are widely detected in the aquatic environment at low concentrations (ng/L to low µg/L), their potential to exert drug-target mediated effects in aquatic species has raised serious concerns. Amitriptyline (AMI) is the most widely used tricyclic ADD, while monoamines, the target of ADDs, are major bioregulators of multiple key physiological processes including feeding, reproduction and behaviour in molluscs. However, the effects of AMI on feeding, reproduction and mating behaviour are unknown in molluscs despite their ecological importance, diversity and reported sensitivity to ADDs. To address this knowledge gap, we investigated the effects of environmentally relevant concentrations of AMI (0, 10, 100, 500 and 1000 ng/L) on feeding, reproduction and key locomotor behaviours, including mating, in the freshwater gastropod, Biomphalaria glabrata over a period of 28 days. To further provide insight into the sensitivity of molluscs to ADDs, AMI concentrations (exposure water and hemolymph) were determined using a novel extraction method. The Fish Plasma Model (FPM), a critical tool for prioritization assessment of pharmaceuticals with potential to cause drug target-mediated effects in fish, was then evaluated for its applicability to molluscs for the first time. Disruption of food intake (1000 ng/L) and reproductive output (500 and 1000 ng/L) were observed at particularly low hemolymph levels of AMI, whereas locomotor behaviours were unaffected. Importantly, the predicted hemolymph levels of AMI using the FPM agreed closely with the measured levels. The findings suggest that hemolymph levels of AMI may be a useful indicator of feeding and reproductive disruptions in wild population of freshwater gastropods, and confirm the applicability of the FPM to molluscs for comparative pharmaceutical hazard identification.

Medical treatment for occipital neuralgia: A comparison between four medications

Introduction: Treatment of Occipital Neuralgia (ON) is challenging and there is no consensus about how to treat it. Current drug therapy is based on different medications from first-line pain-killers up to opioid analgesics but more importantly on antiepileptic medications and classically CARBAMAZEPINE (CA). Methods: In this paper, we present our experience with the medical treatment of ON by comparison of the four most frequently used medications in 133 patients. Results: Analysis of data from our study showed that PREGABALINE (PR) was on average the most effective drug with 60% satisfactory results. AMITRIPTYLINE (AM) with 53.30% ranked second. AM had the highest (14.29%) and GABAPENTINE (GA) had the lowest (8.82%) rates of side effects. Discussion: In this study, we evaluated and compared the efficacy of four medications in the treatment of occipital neuralgia. In first and second-line treatment, the efficacy of PR appears to be higher than CA.

The relationship of sphingolipid mechanisms with oxidative stress and changes in mitochondria during functional unloading of postural muscles

Background. Prolonged inactivity of skeletal muscles is accompanied by the development of oxidative stress and changes in sphingolipid metabolism. The relationship of sphingolipid mechanisms with generation of reactive oxygen species (ROS) in muscles subjected to functional unloading has not been studied.The aim. To identify the relationship between changes in sphingomyelinase and ceramide abundance and ROS production in rat soleus muscle during functional unloading.Methods. Male Wistar rats were subjected to hindlimb suspension for 12 hours or 14 days with the acid sphingomyelinase (ASM) inhibitor amitriptyline (AMI). The levels of ASM, ceramide and ROS were determined by fluorescence microscopy on histological sections. Pro-oxidant enzymes (NADPH oxidases 2 and 4 (NOX2 and NOX4)), cytochrome c oxidase (COX IV), the regulator of mitochondrial biogenesis PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) in muscle homogenates were studied by Western blotting, which also was used for assessment of ceramide and ASM in the isolated mitochondrial fraction. The effects of sphingomyelinase and prooxidants on ceramide, ASM, ROS and NOX2 levels were studied in an ex vivo model by incubating the muscle with exogenous sphingomyelinase or H2O2.Results. 12-hour hindlimb suspension was accompanied by an increase in the level of ASM and ceramide in rat soleus muscle. Unloading for 14 days was characterized by an increase in ASM, ceramide, ROS, NOX2, NOX4 and a decrease in COX IV and PGC-1α levels. ASM and ceramide were also increased in the mitochondrial fraction of muscle. The ASM inhibitor amitriptyline partially or completely prevented the changes caused by the unloading. In the ex vivo model, the stimulating effect of exogenous sphingomyelinase on the ROS and NOX2 levels in rat soleus muscle was found, whereas H2O2 stimulated muscle ASM and ceramide production.Conclusion. A close relationship has been established between the sphingomyeli-nase pathway of ceramide formation and ROS production in skeletal muscle under conditions of functional unloading.

Simultaneous Determination of Amitriptyline Hydrochloride and Propranolol Hydrochloride in Commercial Formulation by Multitudinal UV and Multivariate FT-IR Spectroscopic Methods

Simultaneous Determination of Amitriptyline Hydrochloride and Propranolol Hydrochloride in Commercial Formulation by Multitudinal UV and Multivariate FT-IR Spectroscopic Methods

Transformation mechanisms of antidepressants in biological wastewater treatment: Removal kinetic, transformation products and pathways

The extensive detection of antidepressants in wastewater has raised increasing concerns for human beings. During biological wastewater treatment processes, antidepressants cannot be completely removed and mineralized, which caused the formation of transformation products (TPs). To date, knowledges on TPs that participated in the transformation processes of antidepressants were scarce. To fill this gap, molecular networking nontarget screening based on lab-scale batch assays were employed to explore the removal and transformation of five antidepressants (amitriptyline (AMI), clomipramine (CLO), duloxetine (DUL), nortriptyline (NOR) and paroxetine (PAR)). The removal rate constants per unit of biomass (kbio) of the five antidepressants were found to range from 0.29 to 0.56 L/(gMLSS*d). Comparatively, clomipramine was removed more slowly than other antidepressants, which attributed to its lower electrophilic properties. Subsequently, 22 TPs were tentatively identified, among which 19 ones were newly found in the present study. The proposed transformation pathways indicated that demethylation, N-formylation, N-acetylation, N-succinylation, N-hydroxylation, dealkylation, hydrolysis and nitrosation participated in the transformation of antidepressants in wastewater. Particularly, N-acylation and N-hydroxylation were found as characteristics reactions for antidepressants in wastewater and these reactions consistently occurred at the site of amino functional group, where high electrophilic activity was the dominant causes for the observed characteristics reactions. In silico results revealed that TPs formed during biological wastewater treatment generally had lower toxicity, lower bioaccumulation and higher bioavailability than their parent compounds. Collectively, the present study provides insights into the transformation processes of antidepressants in wastewater, indicating that characteristic transformation reactions occur across different antidepressants, which is theoretically useful to effectively remove pharmaceuticals from wastewater.

Anti-inflammatory effects of khaya senegalensis bark and tinospora cordifolia leaf extracts on striatal ischemic injury in rats

The striatal synaptic pathways play a crucial role in the functioning of the basal ganglia and are an essential part of the cortical-basal ganglia loops that regulate motor function, emotion, and cognition. The purpose of this study was to examine the potential therapeutic benefits of extracts from the leaves of Tinospora cordifolia (TC) and Khaya senegalensis (KS) on striatal ischemia injury resulting from amitriptyline (AMT). Eleven groups (n = 5) comprising fifty-five adult male Wistar rats weighing between 184 and 254 g were created: Distilled water (2 milliliters per kilogram) was used as a control. The groups that included AMT (750 mg/kg), KS (200 mg/kg) + AMT, KS (300 mg/kg) + AMT, KS (400 mg/kg) + AMT; TC (200 mg/kg) + AMT; TC (300 mg/kg) + AMT; TC (400 mg/kg) + AMT; COM (200 mg/kg) + AMT; COM (300 mg/kg) + AMT and COM (400 mg/kg) + AMT. Treatment was given orally for a period of 14 days. Rats were neck dislocated to stop the experiment and brain tissues were removed and preserved in 10% buffered formal saline. TNF- α result showed a significant increase (p&lt;0.05) by 708.9±28.05δ in AMT-treated rats compared to the control (324.8±7.58). And decreased significantly (328.5±5.24α, 380.4±3.43δ and 375.3±5.50δ) in the treated groups compared to AMT-treated rats. Normal cytoarchitecture of the striatal cells was intact in the control group. AMT rates (Ischemic stroke rats) revealed neurodegenerative changes, characterized by cellular hypertrophy and perivascular edema, and proliferation of reactive astrocytes and microglia. However, the treatment of KS, TC, and COM KS+TC remarkably ameliorates striatal cell degeneration by preserving striatal cell cytoarchitecture, especially with COM KS+TC 400 mg/kg treatment. Findings suggest that COM KS+TC possesses anti-inflammatory properties, which could be of potential benefit in the treatment and management of ischemic stroke.

Identification of an Epoxide Metabolite of Amitriptyline In Vitro and In Vivo.

Amitriptyline (ATL), a tricyclic antidepressant, has been reported to cause various adverse effects, particularly hepatotoxicity. The mechanisms of ATL-induced hepatotoxicity remain unknown. The study was performed to identify the olefin epoxidation metabolite of ATL and determine the possible toxicity mechanism. Two glutathione (GSH) conjugates (M1 and M2) and two N-acetylcysteine (NAC) conjugates (M3 and M4) were detected in rat liver microsomal incubations supplemented with GSH and NAC, respectively. Moreover, M1/M2 and M3/M4 were respectively found in ATL-treated rat primary hepatocytes and in bile and urine of rats given ATL. Recombinant P450 enzyme incubations demonstrated that CYP3A4 was the primary enzyme involved in the olefin epoxidation of ATL. Treatment of hepatocytes with ATL resulted in significant cell death. Inhibition of CYP3A attenuated the susceptibility to the observed cytotoxicity of ATL. The metabolic activation of ATL most likely participates in the cytotoxicity of ATL.

Antinociceptive Evaluation of Antidepressants (Cita- lopram, Duloxetine and Amitriptyline) in a Mouse Model of Acute Pain

Introduction: Acute pain is a pervasive and debilitating symptom affecting the general population as well as depressed patients who suffer even more from pain and fatigue. Aims and Objectives: To evaluate the antinociceptive effect induced by antidepressants (Citalopram, Duloxetine and Amitriptyline) in acute pain induced in mice. Place and Duration of study: Animal Research Laboratory of University of Lahore. Study Period: 2018- 2019 Material and Methods: An experimental animal study was carried out on 25 albino mice. The mice were divided into 5 groups; Group 1: Positive Control (PC), Group 2: Ibuprofen (IBO) (Standard) 80mg/kg, Group3: Citalopram (CTP)3mg/kg, Group 4: Duloxetine (DXT) 25mg/kg, Group 5: Amitriptyline (AMT) 15mg/kg. Groups 2-5 were administered drugs orally through a feeding tube as per group designation while Group 1: Control was given an equivalent amount of normal saline. One hour post treatment with test drugs, all Groups (1-5) were injected 10 ml/ kg of 2% acetic acid I/P and number of writhing movements consisting of contraction of abdominal muscles leading to extension of hind limb and periodic arching of body as well as paw licking behavior were counted for 20 minutes at 5- minute interval, using hand tally counter. Degree of analgesia was calculated by using formula of percentage effectiveness. Data was entered and analyzed utilizing SPSS version 21, p?0.05 was taken as significant. Results: Ibuprofen completely eliminated the nociceptive outcome of diluted acetic acid in writhing and licking of experimental animals. Citalopram, showed maximum decreasing effect (95%-96%) in writhing in 5-20 min. However, its effect in paw licking was low. Duloxetine showed 70% to 90% decrease in writhing at 5-20 min whereas 100 % inhibition of paw-licking was observed at 5 to 20 minutes. The writhing effect of amitriptyline was 77%-90% at 5-20 min and paw licking effect was 80-90 % at 5-20 min. Conclusion: Amitriptyline, duloxetine and citalopram have significant effect in reducing the acute nociceptive pain and may be utilized as analgesic in acute state of pain.

Amitriptyline effectiveness in burning mouth syndrome: An in-depth case series analysis.

To assess the effectiveness of amitriptyline (AMT), and to identify the determinants of the treatment's effectiveness in patients diagnosed with burning mouth syndrome (BMS). Treatment of BMS is challenging and no established treatment protocol is available. AMT may be an important treatment option, cout not all patients benefit from this drug. Studies assessing factors related to treatment response are valuable in improving decision-making. This case series study examined the medical records of all patients diagnosed with BMS at an oral medicine unit in a university hospital from 2008 to 2022. The patients were divided into responders to AMT and non-responders to AMT. Data on demographic information, comorbidities, medications, types of symptoms and oral subsites affected were collected. Descriptive and bivariate analyses were conducted to assess the association between the independent variables and the outcome, using the Chi-squared test (P < .05). Three hundred and fourty-nine patients reported a burning mouth sensation, 50 of them (14.3%) being diagnosed with primary BMS. Of these, 35 were treated with AMT, and 26 (74.2%) responded significantly to AMT. All males responded to AMT, whereas only 67.9% of females responded. The mean dose of AMT among responders was 29.8 ± 12.3 mg, with most patients achieving a response with 25 mg (61.5% of patients), followed by 50 mg (23%). The concomitant use of an anticonvulsant resulted in non-response. AMT may be effective in BMS management for most patients.

Comparative Study on the Removal Efficiency of Clomazone and Amitriptyline via Adsorption and Photocatalysis in Aqueous Media: Kinetic Models and Toxicity Assessment.

This study aimed to compare the effectiveness of adsorption and photocatalysis techniques at removing the herbicide clomazone (CLO) and the antidepressant known as amitriptyline (AMI) from water. This study employed kinetic models to analyze the removal processes and assess the potential toxicity of the treated water. The structure and morphology of the prepared multi-walled carbon nanotubes were characterized as adsorbents by transmission electron microscopy, X-ray diffraction, Fourier transform infrared techniques, and Raman spectroscopy. The adsorption kinetics of CLO and AMI were studied on the pristine and functionalized multi-walled carbon nanotubes. Kinetic studies were performed by modeling the obtained experimental data using three kinetic models: pseudo-first-order, pseudo-second-order, and Elovich kinetic models. On the other hand, the efficiency of CLO and AMI photodegradation was examined as a function of the type of irradiation (UV and simulated solar irradiation) and type of TiO2 photocatalyst (Aeroxide and Kronos). Under the experimental conditions employed, the reaction followed pseudo-first-order kinetics. Additionally, in order to assess the toxicity of water containing CLO, AMI, and their intermediates, toxicity assessments were conducted using human fetal lung fibroblast cells. The results obtained indicate the effectiveness of both methods and provide valuable insights into their removal mechanisms, contributing to the advancement of sustainable water treatment strategies.

Spectrophotometric quantification of amitriptyline hydrochloride in pharmaceutical tablets: method development and validation

The development and validation of two uncomplicated, selective, and non-extraction-based visible spectrophotometric methods was carried out for the quantification of a tricyclic antidepressant amitriptyline hydrochloride as pharmaceutical tablets as well as in its pure form. The methods rely on the formation of ion pair complexes between amitriptyline base and two acidic dyes, bromothymol blue and bromocresol purple, which were subsequently measured at 410 and 400 nm, respectively. The developed methods included numerous reaction variables that were examined and improved. Beer's law is applicable under optimal conditions for the bromothymol blue and bromocresol purple methods, respectively, over concentrations from 0.5 to 12.5 μg mL−1 and from 0.5 to 10.0 μg mL−1 amitriptyline hydrochloride. The computed values of molar absorptivity were 1.79 × 104 and 2.32 × 104 L.mol−1.cm−1 for bromothymol blue and bromocresol purple methods, respectively, with Sandell’s sensitivity values of 0.0155 and 0.0119 μg cm−2. Both detection limits and quantification limits were computed and determined to be 0.55 and 1.67 μg mL−1 for bromothymol blue method, and 0.49 and 1.49 μg mL−1 for bromocresol purple method, respectively. The developed methods were successfully applied to estimate the concentration of amitriptyline hydrochloride in bulk form and commercial pills. Therefore, these methods demonstrate promising potential for testing this drug in labs for quality control.Graphical abstractSpectrophotometric quantification of amitriptyline hydrochloride in pharmaceutical tablets: method development and validation

Core-Labeled Reverse Micelle-Based Supramolecular Solvents for Assisted Quick and Sensitive Determination of Amitriptyline in Wastewater.

In recent years, the issue of pharmaceutical contaminants in water bodies has emerged as a significant environmental concern owing to the potential negative impacts on both aquatic ecosystems and human health. Consequently, the development of efficient and eco-friendly methods for their determination and removal is of paramount importance. In this context, the development of a surfactant ensemble sensor has been explored for hard-to-sense amphiphilic drug, i.e., amitriptyline. Herein, a pyrene-based amphiphile chemoreceptor was synthesized and characterized through various spectroscopic techniques such as 1H, 13C NMR, single-crystal XRD, FTIR, and ES-mass spectrometry. Then, dodecanoic acid (DA) and a pyrene-based receptor in a THF/water solvent system were used to generate reverse micelle-based self-aggregates of SUPRAS (SUPRAmolecular Solvent). The structural aspects, such as morphology and size, along with the stability of the SUPRAS aggregates were unfolded through spectroscopic and microscopic insights. The present investigation describes a synergistic approach that combines the unique properties of premicellar concentration of supramolecular solvent with the promising potential of pyrene-based receptor for enhanced amitriptyline extraction with simultaneous determination from water (LOD = 12 nM). To evaluate the effectiveness of the developed aggregates in real-world scenarios, experiments were conducted to determine the sensing efficiency among various pharmaceutical pollutants commonly found in water sources. The results reveal that the synergistic nanoensemble exhibits remarkable sensing ability, toward the amitriptyline (AMT) drug outperforming conventional methods.

MANAGEMENT OF A PATIENT PRESENTED WITH AMITRIPTILINE POISONING- A RARE CASE REPORT

Abstract Tricyclic Antidepressant overdose for suicidal poisoning purpose is not frequent but still possible in patient and his near relative due to its availability at home. On susception laboratory testing is required for many poisons but availability is limited and any delay in diagnosis and starting management may worsen the patient&amp;apos;s condition. Amongst all TCAs, Amitriptyline is classic having sedative and anticholinergic properties. Its self-poisoning is not that much common in general population. Here we are reporting a case of Amitriptyline poisoning in a healthy women aged 30 years brought by relatives with drowsiness and giddiness to our Emergency Medicine Department, LG Hospital, Narendra Modi Medical College, Ahmedabad. Her relatives had given history of self-ingestion of 30 Tab of Amitriptyline Hydrochloride. Each Tablet contained 25 mg of drug molecule. On examination in ED, patient was in drowsy but arousable state. Patient had tachycardia (130/min), high blood pressure (140/90 mm of Hg) and tachypnoea (RR 24/min). Except tachycardia her ECG did not show any significant findings. She was taking Tab. Amitriptyline for her psychiatric problems. Urine sample for toxicology was sent and the reports were normal. Other blood investigations were normal. In emergency room, Ryle&amp;apos;s tube inserted, gastric sample was collected and she was given activated charcoal lavage and force alkaline diuresis with Inj. Furosemide with saline. She was shifted to emergency ICU for further management. After 12 hours patient was conscious and oriented with stable hemodynamic. She was referred to psychiatry department and then transferred to Medicine department for further care. She remained stable there and discharged after 2 days.

Preconcentration and measurement of trace Amitriptyline hydrochloride in water samples using magnetic nanoparticles with dispersive solid‐phase extraction

AbstractIn the separation and determination of trace amounts of drugs in aqueous samples, there is a major challenge in synthesizing highly efficient, cost‐effective, and easy‐to‐use adsorbents based on natural polymers, which are also biocompatible and biodegradable. In the proposed method, magnetite nanoparticles (Fe3O4) on chitosan (as the carrier) modified with β‐cyclodextrin (BCD) were used as a suitable adsorbent for the pre‐concentration and solid‐phase extraction of trace amounts of Amitriptyline HCl (hydrochloride). Ultraviolet spectrophotometer (λ = 236 nm) was the main instrument used for analyte detection and quantification. Moreover, X‐ray diffraction, Fourier transform infrared spectroscopy, Field Emission Scanning Electron Microscopy, and Energy‐Dispersive X‐ray were used for the identification and characterization of the structure and morphology of the adsorbent and to establish the formation of the synthesized magnetic nanosorbents, as well as to confirm the analyte binding to the adsorbent. Experimental variables affecting the extraction/pre‐concentration and determination of the analyte were investigated and optimized; pH of the sample solution, the amount of NaCl salt (in terms of ionic strength of the solution), the amount of adsorbent, temperature, adsorption time, and volume of the eluent (methanol) were the optimized parameters. Finally, the method was successfully applied for the determination of spiked Amitriptyline hydrochloride (HCl) in tap water and human urine samples. Also, High‐Performance Liquid Chromatography was performed on the aqueous samples to compare the proposed method with the USP (the United States Pharmacopeia) standard method of Amitriptyline HCl assay and after performing a t‐test (confidence level of 95%), no significant difference was observed between the two methods. High accuracy and precision (RSD = 3.91%), High analysis speed, few limitations, low expenses, pure extracted analyte, and low waste were the advantages of this method. This method was also compatible with many existing device methods. Under the optimized experimental conditions, the calibration graph was linear in the range of 0.183 to 50 mg.L−1 with a correlation coefficient of 0.996. RSD of the method was 3.91%, the limit of detection was 37.8 µg.L−1, the maximum sorption capacity of the adsorbent for Amitriptyline hydrochloride was 306.525 mg.g−1 and the preconcentration factor was 3.61. Eventually, the proposed method was compared to other methods that have been performed for the determination of Amitriptyline hydrochloride.

Applying children's enuresis treatment with amitriptyline for canine post-spaying urinary incontinence: A pilot estriol-controlled randomized clinical trial

Urinary incontinence due to urethral sphincter mechanism incompetence (USMI) affects up to 20% of bitches that undergo spaying surgery. Amitriptyline is a tricyclic antidepressant whose urinary retention is a reported side effect. This study aimed to assess the efficacy and safety of amitriptyline when compared to estriol orally. Fifteen bitches with a clinical diagnosis of post-spaying UI were evaluated during 60 days in a non-blinded randomized clinical trial. All patients were enrolled after clinical evaluation consisting of anamnesis, physical examination, and complementary exams (complete blood count, biochemical parameters, urinalysis, and abdominal ultrasound). The amitriptyline (AMT) group consisted of 8 bitches, which received the initial dose of 1 mg/kg every 12 h, whereas the estriol (EST) group consisted of 7 bitches which were initially treated with 1 mg/animal every 24 h. Patients underwent clinical evaluation at 7 days, and then at 21 and 60 days of treatment to assess safety and efficacy, as well as adjustments of dose when necessary. A urinary incontinence scale was used to assess the level of incontinence and therapeutic response to treatment. During the period of the study, estriol was fully effective in 71% of cases and amitriptyline in 62%. Both drugs proved safe in the medical treatment of USMI, with adverse effects such as somnolence (AMT, n = 5/8) and male attraction (EST, n = 1/7). The results support the amitriptyline recommendation as a substitute for estriol in USMI treatment.