1,602 results match your criteria Toxicity Selective Serotonin Reuptake Inhibitor


Transformation products of citalopram: Identification, wastewater analysis and in silico toxicological assessment.

Chemosphere 2019 Feb 5;217:858-868. Epub 2018 Nov 5.

Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016, Lisboa, Portugal.

The objective of this study was to identify transformation products (TPs) of citalopram (CIT), an antidepressant drug, in laboratory experiments. Moreover, toxicity predictions and analyzes in wastewater samples were performed. For the formation of TPs, raw water was used for the processes of hydrolysis; photodegradation under ultraviolet (UV) irradiation and chlorination. Read More

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http://dx.doi.org/10.1016/j.chemosphere.2018.11.027DOI Listing
February 2019
7 Reads

Accumulation, metabolite and active defence system responses of fluoxetine in zebrafish embryos: Influence of multiwalled carbon nanotubes with different functional groups.

Aquat Toxicol 2018 Dec 30;205:204-212. Epub 2018 Oct 30.

School of Hydraulic and Ecological Engineering, Nanchang Institute of Technology, Nanchang, 330099, China.

Studies on the bioavailability of organic contaminants adsorbed to nanomaterials are increasing. In this study, we investigated the interaction between fluoxetine (FLX) and three multiwalled carbon nanotubes (MWCNTs) with different functional groups in zebrafish (Danio rerio) embryos, focusing on the FLX accumulation, the formation of the metabolite norfluoxetine (NFLX), and the active defence system responses. The accumulation of FLX in zebrafish was intensified by MWCNTs (46-99%), which simultaneously facilitated the formation of the metabolite NFLX by 23-167%. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0166445X183085
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http://dx.doi.org/10.1016/j.aquatox.2018.10.018DOI Listing
December 2018
9 Reads

Linezolid-associated serotonin toxicity after escitalopram discontinuation: concomitant drug considerations.

BMJ Case Rep 2018 Oct 30;2018. Epub 2018 Oct 30.

College of Pharmacy, University of Florida, Gainesville, Florida, USA.

We report a case of a hospitalised patient who developed probable serotonin toxicity shortly after the initiation of linezolid in whom the selective serotonin reuptake inhibitor (SSRI) escitalopram had been recently discontinued. On day 2 of linezolid administration, the patient reported severe anxiety and was observed to have full body jerking and twitching motions without mental status change. Notably, the patient was concomitantly receiving the antidepressant, trazodone and the benzodiazepine, clonazepam possibly affecting the severity and manifestations of serotonin toxicity. Read More

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http://dx.doi.org/10.1136/bcr-2018-226597DOI Listing
October 2018
4 Reads

Toxicity effects of a novel potent triple reuptake inhibitor, LPM570065, on the fertility and early embryonic development in Sprague-Dawley rats.

Regul Toxicol Pharmacol 2018 Dec 23;100:45-51. Epub 2018 Oct 23.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Yantai University, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, PR China. Electronic address:

Selective serotonin reuptake inhibitors (SSRIs) have developed as novel antidepressants and have been determined to possess higher efficacy and less adverse effects compared to other antidepressants. Our previous studies have showed that LPM570065, a new potent TRI, is relatively nontoxic in acute, subchronic toxicity and genotoxicity evaluations. In the current study, toxicity of LPM570065 was further evaluated on the fertility and early embryonic development in Sprague-Dawley rats. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02732300183027
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http://dx.doi.org/10.1016/j.yrtph.2018.10.008DOI Listing
December 2018
11 Reads

The effect of paroxetine, venlafaxine and bupropion administration alone and combined on spatial and aversive memory performance in rats.

Pharmacol Rep 2018 Dec 21;70(6):1173-1179. Epub 2018 Jul 21.

Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil. Electronic address:

Background: The use of antidepressants in combination is common practice following non-response to single antidepressant agents. Nevertheless, the scientific literature lacks preclinical studies regarding the combined administration of antidepressants across multiple behavioral measures including, but not limited to, cognition. Hence, we aimed to determine the effects of paroxetine (PAR), venlafaxine (VEN) and bupropion (BUP) alone or combined (PAR+BUP or VEN+BUP) on spatial and affective memory tasks to advance the knowledge about the combined use of antidepressants in cognition. Read More

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http://dx.doi.org/10.1016/j.pharep.2018.07.003DOI Listing
December 2018
3 Reads

Demystifying serotonin syndrome (or ).

Can Fam Physician 2018 Oct;64(10):720-727

Assistant Professor and Acting Director of the Doctor of Pharmacy program at the Leslie Dan Faculty of Pharmacy at the University of Toronto in Ontario, an advanced practice hospital pharmacist at the Centre for Addiction and Mental Health in Toronto, a doctoral candidate in the School of Health Professions Education at Maastricht University in the Netherlands, and a research fellow at the Wilson Centre in Toronto.

Objective: To review the symptoms of serotonin toxicity (commonly referred to as ) and the causative drugs and their mechanisms of action, and to equip primary care providers with practical strategies to prevent and identify serotonin toxicity.

Quality Of Evidence: PubMed and Google Scholar were searched for relevant articles on serotonin toxicity, the causes, and the differential diagnosis using search terms related to serotonin toxicity (), causes (individual names of drug classes, individual drug names), and diagnosis (). Experts in psychiatric medicine, psychiatric pharmacy, clinical pharmacology, and medical toxicology were consulted. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6184959PMC
October 2018
4 Reads

Assessing pH-dependent toxicity of fluoxetine in embryonic zebrafish using mass spectrometry-based metabolomics.

Sci Total Environ 2019 Feb 1;650(Pt 2):2731-2741. Epub 2018 Oct 1.

Department of Civil and Environmental Engineering, National University of Singapore, Singapore. Electronic address:

While it is well known that fluoxetine is more toxic to aquatic organisms at high pH, the metabolic dysregulations related to observed pH-dependent effects are still poorly understood. In the present study, we utilized a gas chromatography mass spectrometry (GC-MS) based metabolomics approach to assess metabolomic profile changes in developing zebrafish embryos following exposure (2 hpf-96 hpf) to different concentrations of fluoxetine at three environmentally relevant pH values (7.0, 8. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2018.09.364DOI Listing
February 2019
4 Reads

Impact of the widespread pharmaceutical pollutant fluoxetine on behaviour and sperm traits in a freshwater fish.

Sci Total Environ 2019 Feb 24;650(Pt 2):1771-1778. Epub 2018 Sep 24.

Monash University, School of Biological Sciences, Melbourne 3800, Australia.

Pharmaceutical pollutants are detected in aquatic habitats and wildlife tissues globally. One widespread contaminant of major concern is the antidepressant fluoxetine, which can affect behavioural and physiological processes in non-target species. Despite this, effects of fluoxetine on wildlife behaviour have seldom been investigated across multiple fitness-related contexts, especially at environmentally realistic concentrations. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2018.09.294DOI Listing
February 2019
3 Reads

Modulatory effect of quercetin and its glycosylated form on key enzymes and antioxidant status in rats penile tissue of paroxetine-induced erectile dysfunction.

Biomed Pharmacother 2018 Nov 4;107:1473-1479. Epub 2018 Sep 4.

Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology, P.M.B. 704, Akure, 340001, Nigeria.

This study sought to compare the effects of quercetin and rutin on some enzymes linked to erectile function as well as antioxidant status in penile tissue of paroxetine - induced erectile dysfunction in rats. Animals were randomly divided into twelve groups: normal control (NC), sildenafil (SD), quercetin (QA) (25 and 50 mg/kg), rutin (RU) (25 and 50 mg/kg), PAR (10 mg/kg); PAR + SD; PAR + QA, PAR + RU (25 and 50 mg/kg). After 14 days' treatment, phosphodiesterase-5' (PDE-5'), arginase, adenosine deaminase (ADA), acetylcholinesterase (AChE) and angiotensin-I converting enzyme (ACE) activities as well as malondialdehyde (MDA) and non-protein thiol levels were determined in rat penile tissues. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.08.128DOI Listing
November 2018
6 Reads

Exposure to low concentration of fluoxetine affects development, behaviour and acetylcholinesterase activity of zebrafish embryos.

Comp Biochem Physiol C Toxicol Pharmacol 2019 Jan 6;215:1-8. Epub 2018 Sep 6.

Laboratório de Genética Toxicológica, Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Asa Norte, 70910-900 Brasília, Distrito Federal, Brazil.

Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) antidepressant widely used in clinics and very often found in environmental samples of urban aquatic ecosystems in concentrations ranging from ng/L to μg/L. Fish populations might be especially susceptible to FLX due to the presence of conserved cellular receptors of serotonin. Neurotoxic effects on fish biota of polluted water bodies may be expected, but there are no sufficient studies in the current literature to elucidate this hypothesis. Read More

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http://dx.doi.org/10.1016/j.cbpc.2018.08.009DOI Listing
January 2019
16 Reads

Toxic Effects of Trazodone on Male Reproductive System via Disrupting Hypothalamic-Pituitary-Testicular Axis and Inducing Testicular Oxidative Stress.

Oxid Med Cell Longev 2018 29;2018:7196142. Epub 2018 Jul 29.

Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Anadolu University, Eskisehir, Turkey.

Depression and anxiety are recognized as public health problems. Epidemiological studies have shown that depression and anxiety often occur during reproductive ages between 20 and 60 years of age in males. Trazodone is one of the most frequently prescribed drugs in the treatment of depression and anxiety. Read More

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http://dx.doi.org/10.1155/2018/7196142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087606PMC
December 2018
2 Reads

Effects of waterborne exposure to the antidepressant fluoxetine on swimming, shoaling and anxiety behaviours of the mosquitofish Gambusia holbrooki.

Ecotoxicol Environ Saf 2018 Nov 7;163:646-655. Epub 2018 Aug 7.

Laboratorio de Ecotoxicología Acuática, Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA Ciudad Autónoma de Buenos Aires, Argentina; Instituto de Biodiversidad y Biología Experimental y Aplicada, CONICET-UBA, Ciudad Autónoma de Buenos Aires, Argentina.

Chemical pollution from pharmaceuticals is increasingly recognized as a major hazard to the aquatic biota. Among the wide variety of pharmaceuticals, fluoxetine (FLX) is one of the most widely prescribed antidepressants, and therefore, it is frequently identified in the aquatic environment. As FLX is designed to alter human behaviour and many physiological pathways are conserved across vertebrates, this drug may affect the behaviour of fish living in FLX-polluted environments. Read More

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http://dx.doi.org/10.1016/j.ecoenv.2018.07.085DOI Listing
November 2018
2 Reads

Temporal Profiles and Dose-Responsiveness of Side Effects with Escitalopram and Duloxetine in Treatment-Naïve Depressed Adults.

Behav Sci (Basel) 2018 Jul 17;8(7). Epub 2018 Jul 17.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA.

Side effect profiles of antidepressants are relevant to treatment selection and adherence among patients with major depressive disorder (MDD), but several clinically-relevant characteristics of side effects are poorly understood. We aimed to compare the side effect profiles of escitalopram and duloxetine, including frequencies, time to onset, duration, dose responsiveness, and impact on treatment outcomes. Side effects occurring in 211 treatment-naïve patients with MDD randomized to 12 weeks of treatment with flexibly-dosed escitalopram (10⁻20 mg/day) or duloxetine (30⁻60 mg/day) as part of the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study were evaluated. Read More

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http://dx.doi.org/10.3390/bs8070064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071033PMC
July 2018
17 Reads

Cholecalciferol counteracts depressive-like behavior and oxidative stress induced by repeated corticosterone treatment in mice.

Eur J Pharmacol 2018 Aug 4;833:451-461. Epub 2018 Jul 4.

Laboratório de Avaliação de Substâncias Bioativas, Departamento de Ciências Naturais, Universidade Regional de Blumenau, CEP 89030-903 Blumenau, Santa Catarina, Brazil. Electronic address:

Depression is one of the most frequent neuropsychiatric diseases in the western world and its physiological causes are not yet fully understood. Since the available antidepressants failed to provide a complete illness remission, the diversification of the therapy in the management of depression could be a useful contribution. The present study aimed to investigate the cholecalciferol capability to revert depressive-like behavior induced by chronic corticosterone (CORT) treatment in mice and its implication on the oxidative stress modulation. Read More

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http://dx.doi.org/10.1016/j.ejphar.2018.07.002DOI Listing
August 2018
2 Reads

Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects.

Authors:
Brian A Baldo

Arch Toxicol 2018 Aug 18;92(8):2457-2473. Epub 2018 Jun 18.

Molecular Immunology Unit, Department of Medicine, Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney, University of Sydney, Sydney, NSW, Australia.

Drugs may cause serotonin toxicity by a number of different mechanisms including inhibition of serotonin uptake and metabolism, increased serotonin synthesis and release, activation of serotonin receptors, and inhibition of cytochrome P450 oxidases. Some drug interactions involving opioids can increase intrasynaptic levels of serotonin, and opioid analgesic drugs are now recognized as being involved in some cases of serotonin toxicity especially if administered in conjunction with other serotonergic medications including monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants. In March 2016, the FDA issued a Drug Safety Communication concerning the association of the entire class of opioid pain medicines with serotonin toxicity. Read More

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http://dx.doi.org/10.1007/s00204-018-2244-6DOI Listing
August 2018
11 Reads

The psychostimulant (±)-cis-4,4'-dimethylaminorex (4,4'-DMAR) interacts with human plasmalemmal and vesicular monoamine transporters.

Neuropharmacology 2018 08 23;138:282-291. Epub 2018 Jun 23.

Medical University of Vienna, Center for Physiology and Pharmacology, Institute of Pharmacology, Währingerstraße 13A, 1090, Vienna, Austria; Center for Addiction Research and Science, Medical University Vienna, Waehringerstrasse 13A, 1090 Vienna, Austria. Electronic address:

(±)-cis-4,4'-Dimethylaminorex (4,4'-DMAR) is a new psychoactive substance (NPS) that has been associated with 31 fatalities and other adverse events in Europe between June 2013 and February 2014. We used in vitro uptake inhibition and transporter release assays to determine the effects of 4,4'-DMAR on human high-affinity transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT). In addition, we assessed its binding affinities to monoamine receptors and transporters. Read More

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http://dx.doi.org/10.1016/j.neuropharm.2018.06.018DOI Listing
August 2018
5 Reads

Clomipramine Toxicity in a CYP 2D6 Poor Metabolizer Patient Who Suddenly Stopped Smoking.

J Clin Psychopharmacol 2018 08;38(4):389-391

Department of Clinical Pharmacy St Antonius Hospital Nieuwegein, The Netherlands Department of Clinical Psychiatry St Antonius Hospital Nieuwegein, The Netherlands Department of Clinical Pharmacy St Antonius Hospital Nieuwegein, The Netherlands

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http://dx.doi.org/10.1097/JCP.0000000000000896DOI Listing
August 2018
2 Reads

Fluoxetine Inhibits Canonical Wnt Signaling to Impair Embryoid Body Morphogenesis: Potential Teratogenic Mechanisms of a Commonly Used Antidepressant.

Toxicol Sci 2018 Oct;165(2):372-388

Developmental and Reproductive Biology Graduate Program, Institute for Biogenesis Research, University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii 96813.

Fluoxetine is one of the most commonly prescribed antidepressants in the selective serotonin reuptake inhibitor (SSRI) class. Epidemiologic studies have suggested a link between maternal fluoxetine use during pregnancy and an increased incidence of birth defects. However, the mechanisms by which fluoxetine adversely impacts embryonic developments are unknown. Read More

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http://dx.doi.org/10.1093/toxsci/kfy143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154268PMC
October 2018
8 Reads

In vivo investigation on the chronic hepatotoxicity induced by sertraline.

Environ Toxicol Pharmacol 2018 Jul 30;61:107-115. Epub 2018 May 30.

Department of Biological Sciences, College of Science, Jerash University, Jordan. Electronic address:

Although sertraline is widely prescribed as relatively safe antidepressant drug, hepatic toxicity was reported in some patients with sertraline treatment. The present study was conducted to investigate the morphometric, hepatotoxicity, and change in gene expression of drug metabolizing enzymes. Male healthy adult rabbits (Oryctolagus cuniculus) ranging from 1050 to 1100 g were exposed to oral daily doses of sertraline (0, 1, 2, 4, 8 mg/kg) for 9 weeks. Read More

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http://dx.doi.org/10.1016/j.etap.2018.05.021DOI Listing
July 2018
4 Reads

Successful intravenous lipid emulsion therapy: Olanzapine intoxication.

Acute Med 2018 ;17(2):96-97

Haseki Training and Research Hospital, Department of Emergency Medicine, Istanbul, Turkey.

Olanzapine is an antipsychotic drug used in psychiatric diseases. At high doses it exhibits cardiovascular and neurological sideeffects in particular. Lipid emulsion therapy for the removal of medication from plasma in high-dose lipophilic drug use has recently become very widespread. Read More

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October 2018
8 Reads

Toxicological Assessment of Venlafaxine: Acute and Subchronic Toxicity Study in Rats.

Int J Toxicol 2018 Jul/Aug;37(4):327-334. Epub 2018 Jun 3.

3 Psychiatry Department, Faculty of Medicine, Minia University, Menia, Egypt.

Antidepressants are the most commonly prescribed drugs for psychiatric treatment, and venlafaxine (VEN) is one of the most popular options. Venlafaxine is a nontricyclic dual-acting serotonin-norepinephrine reuptake inhibitor. Although an increased incidence of acute toxicity and addiction has been reported, controlled studies examining its toxic effects on different organs are still lacking. Read More

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http://dx.doi.org/10.1177/1091581818777470DOI Listing
June 2018
40 Reads
1.233 Impact Factor

Inhibitory effects of fluoxetine, an antidepressant drug, on masseter muscle nociception at the trigeminal subnucleus caudalis and upper cervical spinal cord regions in a rat model of psychophysical stress.

Exp Brain Res 2018 08 28;236(8):2209-2221. Epub 2018 May 28.

Division of Oral Physiology, Niigata University Graduate School of Medical and Dental Sciences, 2-5274, Gakkocho-Dori, Chuo-ku, Niigata, 951-8514, Japan.

This study aimed to determine whether psychophysical stress conditionings had facilitatory effects on masseter muscle nociception in the central nervous system via serotonergic mechanisms in rats. Two experiments were conducted to assess: (1) whether repeated forced swim stress for 3 days increased the number of Fos-positive neurons evoked by masseter muscle injury due to formalin injection; and (2) whether serotonin-reuptake inhibitor, fluoxetine, administered daily after each stress conditioning, had modulatory roles on Fos expression. The number of Fos-positive cells was quantified in several areas within the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord regions (Vc areas), including the ventrolateral area of the trigeminal subnucleus interpolaris/Vc transition, and the middle or caudal portion of the Vc regions, since nociceptive neural activity in the Vc region could play critical roles in deep craniofacial nociception. Read More

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http://dx.doi.org/10.1007/s00221-018-5297-0DOI Listing
August 2018
2 Reads

Effects of acute and chronic exposures of fluoxetine on the Chinese fish, topmouth gudgeon Pseudorasbora parva.

Ecotoxicol Environ Saf 2018 Sep 21;160:104-113. Epub 2018 May 21.

Key Laboratory of Pollution Ecology and Environmental Engineering, Institute of Applied Ecology, Chinese Academy of Sciences, 110016, China. Electronic address:

Fluoxetine is a selective serotonin reuptake inhibitor used as an antidepressant and has been frequently detected in aquatic environments. However, its effects in fish from Asia remain relatively less studied. In this study, the topmouth gudgeon Pseudorasbora parva was exposed to 0, 50, and 200 µg/L of fluoxetine for 4 h and 42 d. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01476513183035
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http://dx.doi.org/10.1016/j.ecoenv.2018.04.061DOI Listing
September 2018
5 Reads

Environmentally relevant concentrations of tramadol and citalopram alter behaviour of an aquatic invertebrate.

Aquat Toxicol 2018 Jul 14;200:226-232. Epub 2018 May 14.

University of South Bohemia in České Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zátiší 728/II, Vodňany, 389 25, Czech Republic.

Environmental pollution by pharmaceutically active compounds, used in quantities similar to those of pesticides and other organic micropollutants, is increasingly recognized as a major threat to the aquatic environment. These compounds are only partly removed from wastewaters and, despite their low concentrations, directly and indirectly affect behaviour of freshwater organisms in natural habitats. The aim of this study was to behaviourally assess the effects of an opioid painkiller (tramadol) and antidepressant drug (citalopram) on behaviour patterns of a clonal model species, marbled crayfish. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0166445X183042
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http://dx.doi.org/10.1016/j.aquatox.2018.05.008DOI Listing
July 2018
11 Reads

Effects of waterborne antidepressants on non-target animals living in the aquatic environment: A review.

Sci Total Environ 2018 Aug 16;631-632:789-794. Epub 2018 Mar 16.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. Electronic address:

After application, antidepressants, like other pharmaceuticals, are excreted from human body in their native form or as metabolites and enter the aquatic environment via different pathways. As concentrations of antidepressant residues in water continue to increase, their effects on non-target animals are being discussed. The aim of this study is to summarize current knowledge about the effects of wateborne antidepressants on non-target animals living in surface waters - invertebrates, fish and amphibians. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2018.03.076DOI Listing
August 2018
18 Reads

In vitro and in vivo drug combination for the treatment of Trypanosoma cruzi infection: A multivariate approach.

Exp Parasitol 2018 Jun 18;189:19-27. Epub 2018 Apr 18.

Instituto de Investigaciones en Ciencias de la Salud (INICSA) UNC-CONICET, Centro de Estudios e Investigación de la Enfermedad de Chagas y Leishmaniasis, Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Santa Rosa 1085, Córdoba X5000ESU, Argentina. Electronic address:

Combination therapies based on the available drugs have been proposed as promising therapeutic alternatives for many diseases. Clomipramine (CLO) has been found to modify the evolution of the experimental infection. The objective of this study was to evaluate the combined effect of benznidazole (BZ) and clomipramine (CLO) against different life-stages of Trypanosoma cruzi in vitro and their efficacy in a murine model. Read More

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http://dx.doi.org/10.1016/j.exppara.2018.04.016DOI Listing
June 2018
8 Reads

Prospective environmental risk assessment of mixtures in wastewater treatment plant effluents - Theoretical considerations and experimental verification.

Water Res 2018 09 14;140:56-66. Epub 2018 Apr 14.

UBA - German Environment Agency, Wörlitzer Platz 1, 06844 Dessau-Roßlau, Germany.

The aquatic environment is continually exposed to a complex mixture of chemicals, whereby effluents of wastewater treatment plants (WWTPs) are one key source. The aim of the present study was to investigate whether environmental risk assessments (ERAs) addressing individual substances are sufficiently protective for such coincidental mixtures. Based on a literature review of chemicals reported to occur in municipal WWTP effluents and mode-of-action considerations, four different types of mixtures were composed containing human pharmaceuticals, pesticides, and chemicals regulated under REACH. Read More

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http://dx.doi.org/10.1016/j.watres.2018.04.031DOI Listing
September 2018
5 Reads

Does fluoxetine exposure affect hypoxia tolerance in the Gulf toadfish, Opsanus beta?

Aquat Toxicol 2018 Jun 23;199:55-64. Epub 2018 Mar 23.

Rosenstiel School of Marine and Atmospheric Science, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33149, USA. Electronic address:

Due to ineffective wastewater treatment technologies, pharmaceuticals such as the selective serotonin reuptake inhibitors (SSRIs)-a common class of antidepressants which inhibit the serotonin transporter (SERT)-can be found in surface waters and marine receiving waters near wastewater effluents. Understanding how exposure to these chemicals might impact non-target organisms, especially combined with other environmental stressors like hypoxia, is essential in order to thoroughly evaluate environmental risk. It was hypothesized that both acute and chronic exposure to the SSRI fluoxetine (FLX) would interfere with the metabolic hypoxia response of the Gulf toadfish, Opsanus beta. Read More

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http://dx.doi.org/10.1016/j.aquatox.2018.03.023DOI Listing
June 2018
5 Reads

The antidepressant fluoxetine alters mechanisms of pre- and post-copulatory sexual selection in the eastern mosquitofish (Gambusia holbrooki).

Environ Pollut 2018 Jul 20;238:238-247. Epub 2018 Mar 20.

School of Biological Sciences, Monash University, Victoria, Australia; Department of Biosciences, Åbo Akademi University, Turku, Finland.

Contamination of aquatic habitats with pharmaceuticals is a major environmental concern. Recent studies have detected pharmaceutical pollutants in a wide array of ecosystems and organisms, with many of these contaminants being highly resistant to biodegradation and capable of eliciting sub-lethal effects in non-target species. One such pollutant is fluoxetine, a widely prescribed antidepressant, which is frequently detected in surface waters globally and can alter physiology and behaviour in aquatic organisms. Read More

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http://dx.doi.org/10.1016/j.envpol.2018.03.006DOI Listing
July 2018
2 Reads

The effects of fluoxetine on attachment and righting behaviours in marine (Gibbula unbilicalis) and freshwater (Lymnea stagnalis) gastropods.

Ecotoxicology 2018 May 9;27(4):477-484. Epub 2018 Mar 9.

Institute of Marine Sciences, School of Biological Sciences, University of Portsmouth, Ferry Road, Portsmouth, PO4 9LY, UK.

Recent studies have highlighted that antidepressants such as the selective serotonin reuptake inhibitors (SSRIs) entering aquatic systems through wastewater discharges might impact organisms at environmentally relevant concentrations. In this study, two snail species (Gibbula unbilicalis and Lymnea stagnalis) representing the marine and freshwater environments were exposed to a large range of fluoxetine concentrations (1 ng L-1 mg L) and two distinct behaviours (foot detachment and righting time) were recorded. Fluoxetine significantly caused foot detachment only at the higher of the concentrations (1 mg L) in both species during the course of this short term 1. Read More

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http://dx.doi.org/10.1007/s10646-018-1919-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897494PMC
May 2018
2 Reads

Overdoses and Substance Toxicity in Patients Admitted to Intensive Care Units in a Midwestern U.S. City.

J Trauma Nurs 2018 Mar/Apr;25(2):87-91

Internal Medicine Residency Program, University of Iowa-Des Moines (Drs Schuring, Dodge, Whitcomb, Wall, and Smith); College of Pharmacy and Health Sciences, Drake University, Des Moines, Iowa (Dr Wall); and Pulmonary and Critical Care Medicine, The Iowa Clinic, Des Moines, Iowa (Dr Hicklin).

Toxic exposures with serious outcomes have increased over the last decade. Limited data exists on the pattern and outcomes of overdose-exposure patients requiring intensive care unit (ICU) admission. The primary objective of this study was to characterize the causes, treatments, and outcomes of toxic exposures in a mid-sized Midwestern health system. Read More

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http://dx.doi.org/10.1097/JTN.0000000000000349DOI Listing
September 2018
8 Reads

Combined treatment with a selective PDE10A inhibitor TAK-063 and either haloperidol or olanzapine at subeffective doses produces potent antipsychotic-like effects without affecting plasma prolactin levels and cataleptic responses in rodents.

Pharmacol Res Perspect 2018 02;6(1)

CNS Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.

Activation of indirect pathway medium spiny neurons (MSNs) via promotion of cAMP production is the principal mechanism of action of current antipsychotics with dopamine D receptor antagonism. TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one] is a novel phosphodiesterase 10A inhibitor that activates both direct and indirect pathway MSNs through increasing both cAMP and cGMP levels by inhibition of their degradation. The activation of indirect pathway MSNs through the distinct mechanism of action of these drugs raises the possibility of augmented pharmacological effects by combination therapy. Read More

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http://dx.doi.org/10.1002/prp2.372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817828PMC
February 2018
5 Reads

Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

Pharmacol Biochem Behav 2018 03 31;166:27-34. Epub 2018 Jan 31.

Departamento de Biología de la Reproducción, Universidad Autónoma Metropolitana-Iztapalapa, Apartado Postal 55 535, C.P. 09340 Ciudad de México, Mexico. Electronic address:

Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e. Read More

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http://dx.doi.org/10.1016/j.pbb.2018.01.004DOI Listing
March 2018
1 Read

Anti-Oxidative Effects of Melatonin Receptor Agonist and Omega-3 Polyunsaturated Fatty Acids in Neuronal SH-SY5Y Cells: Deciphering Synergic Effects on Anti-Depressant Mechanisms.

Mol Neurobiol 2018 Sep 3;55(9):7271-7284. Epub 2018 Feb 3.

Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical UniversityHospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.

Omega-3 polyunsaturated fatty acids (n-3 or omega-3 PUFAs) and melatonin receptor agonist ramelteon (RMT) both display antidepressant effects, while their cellular effects on anti-oxidative and neuroprotective mechanisms might be different. In this study, we aimed to decipher the individual and synergistic actions of n-3 PUFAs and RMT, as compared with the conventional antidepressant fluoxetine (FLX), in a cellular model of oxidative stress, which might play an important role in the pathophysiology of depression and associated disorders. We investigated the rescue and prevention effects of FLX, RMT, and n-3 PUFAs, e. Read More

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http://link.springer.com/10.1007/s12035-018-0899-x
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http://dx.doi.org/10.1007/s12035-018-0899-xDOI Listing
September 2018
13 Reads

Joint effects of nine antidepressants on Raphidocelis subcapitata and Skeletonema marinoi: A matter of amine functional groups.

Aquat Toxicol 2018 Mar 31;196:117-123. Epub 2018 Jan 31.

CERMN, UFR des Sciences Pharmaceutiques, UPRES EA4258 - FR CNRS INC3 M - SF 4206 ICORE, Université de Caen Basse-Normandie, Bd Becquerel, Caen cedex 14032, France; Ifremer, LER, Station de Port en Bessin, Avenue du Général de Gaulle BP 32, Port en Bessin 14520, France.

Antidepressants are among the most prescribed pharmaceuticals throughout the world. Their presence has already been detected in several aquatic ecosystems worldwide and their effects on non-target organisms justify the growing concern of both the public and regulatory authorities. These emerging pollutants do not occur as isolated compounds but rather as multi-component mixtures, which may lead to increased adverse effects compared to individual compounds. Read More

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http://dx.doi.org/10.1016/j.aquatox.2018.01.015DOI Listing
March 2018
5 Reads

Behaviour of freshwater snails (Radix balthica) exposed to the pharmaceutical sertraline under simulated predation risk.

Ecotoxicology 2018 Mar 18;27(2):144-153. Epub 2018 Jan 18.

Aquatic Ecology, Department of Biology, Lund University, Ecology Building, Lund, 223 62, Sweden.

Due to their potential for affecting the modulation of behaviour, effects of selective serotonin reuptake inhibitors (SSRIs) in the environment are particularly interesting regarding interspecies interactions and non-consumptive effects (NCEs) induced by predator cues in prey organisms. We evaluated the effects of sertraline (0.4, 40 ng/L, 40 µg/L) over 8 days on activity and habitat choice in the freshwater snail Radix balthica, on snails' boldness in response to mechanical stimulation (simulating predator attack), and their activity/habitat choice in response to chemical cues from predatory fish. Read More

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http://dx.doi.org/10.1007/s10646-017-1880-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847023PMC
March 2018
4 Reads

Trichloroethylene perturbs HNF4a expression and activity in the developing chick heart.

Toxicol Lett 2018 Mar 4;285:113-120. Epub 2018 Jan 4.

Department of Cellular & Molecular Medicine, University of Arizona, Tucson, AZ 85724-5044, United States. Electronic address:

Exposure to trichloroethylene (TCE) is linked to formation of congenital heart defects in humans and animals. Prior interactome analysis identified the transcription factor, Hepatocyte Nuclear Factor 4 alpha (HNF4a), as a potential target of TCE exposure. As a role for HNF4a is unknown in the heart, we examined developing avian hearts for HNF4a expression and for sensitivity to TCE and the HNF4a agonist, Benfluorex. Read More

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http://dx.doi.org/10.1016/j.toxlet.2017.12.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803365PMC
March 2018
11 Reads

Fenfluramine-Phentermine is Associated with an Increase in Cellular Proliferation Ex Vivo and In Vitro.

J Heart Valve Dis 2017 07;26(4):467-471

Division of Biochemistry and Molecular Biology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA.

Background And Aim Of The Study: Fenfluraminephentermine (FenPhen) has been implicated in accelerated valvular heart disease, characterized by valvular regurgitation and thickening, and resembling the histopathologic lesions found in carcinoid. The study aim was to determine whether cellular proliferation is present in FenPhen-exposed valves, by utilizing an in-vitro model to test whether FenPhen has a direct mitogenic effect on cardiac valvular cells, as compared to serotonin.

Methods: Ex-vivo valves were tested for proliferation in surgically removed FenPhen-exposed valves (n = 10) and compared to proliferation levels in normal human cardiac valves removed at autopsy (n = 10). Read More

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July 2017
17 Reads

Influence of photolabile pharmaceuticals on the photodegradation and toxicity of fluoxetine and fluvoxamine.

Environ Sci Pollut Res Int 2018 Mar 21;25(7):6890-6898. Epub 2017 Dec 21.

Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha Street, 02-097, Warsaw, Poland.

Pharmaceuticals in the aquatic environment may be decomposed by abiotic and biotic factors. Photodegradation is the most investigated abiotic process, as it occurs in the natural environment and may be applied in wastewater treatment technology. Although pharmaceuticals are detected in effluents and surface water in a mixture, the photodegradation process is mainly evaluated with single compounds. Read More

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http://dx.doi.org/10.1007/s11356-017-0973-3DOI Listing
March 2018
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Systematic screening of generic drugs for progressive multiple sclerosis identifies clomipramine as a promising therapeutic.

Nat Commun 2017 12 19;8(1):1990. Epub 2017 Dec 19.

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, T2N 4N1, Canada.

The treatment of progressive multiple sclerosis (MS) is unsatisfactory. One reason is that the drivers of disease, which include iron-mediated neurotoxicity, lymphocyte activity, and oxidative stress, are not simultaneously targeted. Here we present a systematic screen to identify generic, orally available medications that target features of progressive MS. Read More

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http://dx.doi.org/10.1038/s41467-017-02119-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736601PMC
December 2017
24 Reads

Psychotropics and Male Reproduction.

Adv Exp Med Biol 2017 ;1034:63-101

Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA.

Psychotropic drugs, including antidepressants, antipsychotics, and anticonvulsants, all have negative effects on sexual function and semen quality. These adverse events vary among men and are less pronounced for some medications, allowing their effects to be managed to some extent. Use of specific serotonin reuptake inhibitors (SSRIs) is prevalent in men of reproductive age; and application to treat premature ejaculation increases the number of young men on SSRI therapy. Read More

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http://dx.doi.org/10.1007/978-3-319-69535-8_8DOI Listing
June 2018
12 Reads

Alleviating the hepatotoxicity of trazodone via supramolecular encapsulation.

Food Chem Toxicol 2018 Feb 14;112:421-426. Epub 2017 Dec 14.

State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China. Electronic address:

In order to develop a novel strategy to alleviate the inherent hepatotoxicity of antidepressant trazodone (TZ), Cucurbit[7]uril (CB[7]) was adopted as pharmaceutical excipients and was studied for its capability to reduce the hepatotoxicity of TZ via supramolecular encapsulation. CB[7] was found to form strong 1:1 host-guest complexes with TZ and its metabolite m-chlorophenyl piperazine (mCPP), with binding constants of 1.50 (±0. Read More

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http://dx.doi.org/10.1016/j.fct.2017.12.016DOI Listing
February 2018
8 Reads

Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents.

Int J Mol Sci 2017 Dec 5;18(12). Epub 2017 Dec 5.

Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and is shown to be effective against pain. However, whether and how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not clearly understood. Read More

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http://dx.doi.org/10.3390/ijms18122626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751229PMC
December 2017
6 Reads

Real Patient and its Virtual Twin: Application of Quantitative Systems Toxicology Modelling in the Cardiac Safety Assessment of Citalopram.

AAPS J 2017 11 27;20(1). Epub 2017 Nov 27.

Simcyp Limited, a Certara Company, Blades Enterprise Centre, John Street, Sheffield, S2 4SU, UK.

A quantitative systems toxicology (QST) model for citalopram was established to simulate, in silico, a 'virtual twin' of a real patient to predict the occurrence of cardiotoxic events previously reported in patients under various clinical conditions. The QST model considers the effects of citalopram and its most notable electrophysiologically active primary (desmethylcitalopram) and secondary (didesmethylcitalopram) metabolites, on cardiac electrophysiology. The in vitro cardiac ion channel current inhibition data was coupled with the biophysically detailed model of human cardiac electrophysiology to investigate the impact of (i) the inhibition of multiple ion currents (I, I, I); (ii) the inclusion of metabolites in the QST model; and (iii) unbound or total plasma as the operating drug concentration, in predicting clinically observed QT prolongation. Read More

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http://dx.doi.org/10.1208/s12248-017-0155-8DOI Listing
November 2017
10 Reads

Synergy effects of fluoxetine and variability in temperature lead to proportionally greater fitness costs in Daphnia: A multigenerational test.

Aquat Toxicol 2017 Dec 8;193:268-275. Epub 2017 Nov 8.

Department of Biology & CESAM - Centre for Environmental and Marine Studies, University of Aveiro, Campus Universitário Santiago, 3810-193 Aveiro, Portugal. Electronic address:

Increased variability in water temperature is predicted to impose disproportionally greater fitness costs than mean increase in temperature. Additionally, water contaminants are currently a major source of human-induced stress likely to produce fitness costs. Global change models forecast an increase in these two human-induced stressors. Read More

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http://dx.doi.org/10.1016/j.aquatox.2017.10.017DOI Listing
December 2017
13 Reads

A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors.

Cancer Chemother Pharmacol 2018 01 3;81(1):73-80. Epub 2017 Nov 3.

Department of Oncology, Rigshospitalet, Blegsdamsvej 9, 2100, Copenhagen, Denmark.

Purpose: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors.

Methods: Non-smoking patients of ≥ 18 years with advanced solid tumors, excluding breast cancer, were included. Read More

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http://link.springer.com/10.1007/s00280-017-3469-4
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http://dx.doi.org/10.1007/s00280-017-3469-4DOI Listing
January 2018
18 Reads

Developmental exposure to the SSRI citalopram causes long-lasting behavioural effects in the three-spined stickleback (Gasterosteus aculeatus).

Ecotoxicology 2018 Jan 23;27(1):12-22. Epub 2017 Oct 23.

School of Natural Sciences, Technology and Environmental Studies, Södertörn University, Alfred Nobels allé 7, SE-141 89, Huddinge, Sweden.

Selective Serotonin re-uptake inhibitors (SSRIs) are a class of psychotropic drugs used to treat depression in both adolescents and pregnant or breast-feeding mothers as well as in the general population. Recent research on rodents points to long-lasting behavioural effects of pre- and perinatal exposure to SSRIs which last into adulthood. In fish however, studies on effects of developmental exposure to SSRIs appears to be non-existent. Read More

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http://dx.doi.org/10.1007/s10646-017-1866-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758650PMC
January 2018
19 Reads

Social hierarchy modulates responses of fish exposed to contaminants of emerging concern.

PLoS One 2017 19;12(10):e0186807. Epub 2017 Oct 19.

Aquatic Toxicology Laboratory, Saint Cloud State University, Saint Cloud, Minnesota, United States of America.

Many organisms, including the fathead minnow (Pimephales promelas), a toxicological model organism, establish social hierarchies. The social rank of each male in a population is under the control of the hypothalamic-pituitary-gonadal (HPG) axis mainly through regulation of circulating androgen concentrations, which in turn drive the expression of secondary sex characteristics (SSCs). As dominant and subordinate males in an exposure study are initially under different physiological conditions (i. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186807PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648243PMC
November 2017
4 Reads