Pharmacology Commons^™

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Safety Of Potentised Dilutions Of Rhus Toxicodendron In Wistar Albino Rats, Abanti Goswami, Narasimha Kumar Gv, Vara Prasad Saka, Pankaj Gupta, Bibaswan Biswas, Digvijay Verma

Indian Journal of Research in Homoeopathy

Background: Rhus toxicodendron (Rhus tox.) is a well-known homoeopathic medicine used to treat inflammatory disorders supported by historical and modern scientific evidence. Objective: The safety testing of 6C, 30C and 200C potencies of Rhus tox. through acute and sub-acute oral toxicity tests as per the Organisation for Economic Cooperation and Development test guidelines. Methods: For the acute oral toxicity study, Rhus tox. (2000 μL/kg) was administered to rats and observed for 14 days. For the subacute oral toxicity study, Rhus tox. (200 μL/kg) was administered for 28 days and additional recovery groups were included to monitor reversibility, persistence, or delayed …

Pediatric Beta Blocker Therapy: A Comprehensive Review Of Development And Genetic Variation To Guide Precision-Based Therapy In Children, Adolescents, And Young Adults., Mollie Walton, Jonathan B. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Beta adrenergic receptor antagonists, known as beta blockers, are one of the most prescribed medications in both pediatric and adult cardiology. Unfortunately, most of these agents utilized in the pediatric clinical setting are prescribed off-label. Despite regulatory efforts aimed at increasing pediatric drug labeling, a majority of pediatric cardiovascular drug agents continue to lack pediatric-specific data to inform precision dosing for children, adolescents, and young adults. Adding to this complexity is the contribution of development (ontogeny) and genetic variation towards the variability in drug disposition and response. In the absence of current prospective trials, the purpose of this comprehensive review …

An Acute Herb-Drug Interaction Of Magnoliae Officinalis Cortex With Methotrexate Via Inhibiting Multidrug Resistance-Associated Protein 2, Chung-Ping Yu, Pei-Ying Li, Szu-Yu Chen, Shiuan-Pey Lin, Ying-Chen Chen, Lu-Ching Ho, Yow-Wen Hsieh, Yu-Chi Hou

Journal of Food and Drug Analysis

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX …

An Auxiliary Strategy Of Partial Least Squares Regression In Pharmacokinetic/Pharmacodynamic Studies: A Case Of Application Of Guhong Injection In Myocardial Ischemia/Reperfusion Rats, Hai-Yang Chen, Chang Li, Chong-Yu Shao, Yu-Jia Wu, Hai-Tong Wan, Yu He

Journal of Food and Drug Analysis

Guhong injection (GHI) has been applied in the therapy of cardio-cerebrovascular disease in clinic, but there is no report about the pharmacokinetic/pharmacodynamic (PK/PD) research on GHI treating myocardial ischemia/reperfusion (MI/R) injury in rats. In this study, eight compounds of GHI in plasma, including N-acetyl-L-glutamine (NAG), chlorogenic acid (CGA), hydroxysafflor yellow A (HSYA), p-coumaric acid (pCA), rutin, hyperoside, kaempferol-3-O-rutinoside, and kaempferol-3-O-glucoside, were quantified by LC-MS/MS. We discovered that the values of t_1/2β, k₁₂, V₂, and CL₂ were larger than those of t_1/2α, k₂₁, V₁, and …

Ionizable Copolymer Functionalized Magnetic Nanocomposite As An Adsorbent For Boosting The Extraction Selectivity Of Aristolochic Acids, Qi-Yue Xie, Yang Chen, Chang-Jun Li, Jia-Bin Zhang, Xiu-Jun Cao, Jun Lu

Journal of Food and Drug Analysis

Aristolochic acid nephropathy (AAN) has drawn increasing public attention. Organic anion transporters (OATs) are considered to be responsible for mediating nephrotoxicity of aristolochic acids (AAs), as AAs are typical OAT1 substrates that exhibit anionic properties and contain one hydrophobic domain. Inspired by the OAT1 three-dimensional structure or substrate/protein interactions involved in transport, we designed a magnetic polymeric hybrid, mimicking the effect of basic and aromatic residues of OAT1, for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in Traditional Chinese patent medicines (TCPM). N, N-dimethylaminopropyl acrylamide (DMAPAm) was used as a cationic monomer and copolymerized …

Effect Of Indian Gooseberry Extract On Improving Methylglyoxal-Associated Leptin Resistance In Peripheral Tissues Of High-Fat Diet-Fed Rats, Sheng-Yi Chen, Yue-Ning Huang, Jer-An Lin, Gow-Chin Yen

Journal of Food and Drug Analysis

Increased leptin resistance and methylglyoxal (MG) levels are observed in obese patients. However, whether MG deposits contribute to leptin resistance, oxidative stress, and inflammation in peripheral tissues remains unclear. In addition, the edible fruit of Indian gooseberry (Phyllanthus emblica L.) contains abundant bioactive components such asvitamin C, β-glucogallin (β-glu), gallic acid (GA), and ellagic acid (EA). Water extract of Indian gooseberry fruit (WEIG) and GA has been shown to improve cognitive decline by suppressing brain MG-induced insulin resistance in rats administered a high-fat diet (HFD). Accordingly, this study investigated the functions of WEIG and GA in inhibiting MG-induced leptin …

Pomelo (Citrus Grandis (L.) Osbeck) Sponge Layers As A Potential Source Of Soluble Dietary Fiber: Evaluation Of Its Physicochemical, Structural And Functional Properties, Xiaowei Chen, Jiajia Chen, Jian Peng, Yuanshan Yu, Jijun Wu, Jing Wen, Zhiying Kang, Yanhui Wang, Yujuan Xu, Lu Li

Journal of Food and Drug Analysis

Pomelo sponge layer (PSL) had been considered as a potential source of soluble dietary fiber (SDF), while they were mostly disposed of as waste. To promote high-value utilization of pomelo wastes, this study extracted SDF from PSL of six varieties of pomelo, and their physicochemical, structural and functional properties were investigated. Results indicated that all PSL-SDFs showed good physicochemical and functional properties. Among them, PSL-SDF from grapefruit (GRSDF) showed better water holding capacity and swelling capacity, whereas Shatian pomelo PSL-SDF and Guanxi pomelo PSL-SDF had the highest thermal stability and oil holding capacity, respectively. Furthermore, compared with other PSL-SDFs, GRSDF …

Trans-2-Nonadecyl-4-(Hydroxymethyl)-1,3-Dioxolane (Tnhd) Purified From Freshwater Clams Markedly Alleviates Dimethylnitrosamine-Induced Hepatic Fibrosis, Ya-Ru Kuo, Chen-Yu Tsai, Wei-Sheng Lin, Chi-I Chang, Ching-Shu Lai, Min-Hsiung Pan

Journal of Food and Drug Analysis

Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression …

Evaluation Of Novel Therapeutic Agents For The Treatment Of Chronic Dry Eyes, Lilian Huynh, Evonie Villarete, Surajit Dey

Annual Research Symposium

Dry eye disease (DED) is a multifactorial ocular condition, where disrupted tear film stability and ocular surface inflammation affected between 5% to 34% of the worldwide population in 2015 and posed a challenge to conventional ophthalmic treatments. Recent advances have led to potential novel therapeutics aiming to alleviate symptoms and improve patient outcomes.

The Effect Of Caffeine On Bee Behavior: A Progressive Ratio Study, Kayle Cohen, Becky Hansis-O'Neill, Aimee Dunlap Dr

Undergraduate Research Symposium

This presentation focuses on the effect of caffeine on bee behavior using behavioral pharmacology methodologies. Researchers trained bumblebees to drink out of artificial flowers, then administered sucrose nectar or caffeinated sucrose nectar during a schedule of progressive and fixed ratios. The finding suggests that caffeine did increase the number of rewards during the fixed ratio, but not in the progressive ratio. However, research is still ongoing as bees continue to be tested..

Heavy Metals Analysis And Physicochemical Characterization Of Groundwater At A Battery Recycling Site In South-Western Nigeria, Adeniyi T. Adeleke, Rasaki K. Odunaike, Shamsideen K. Alausa, Idris O. Olayiwola, Adetoro T. Talabi, Qasim A. Adeniji, Adejumobi C. Adeniyi

Tanzania Journal of Science

Indiscriminate dumping of battery waste is a huge issue that endangers human health and the environment. This study aimed at analysing the health impacts of exposure to pollution from spent battery recycling in Ogun State, which houses a diverse range of battery recycling industries. At this study site, forty water samples were studied over the Wet and Dry seasons to assess the impact of battery recycling waste on groundwater. Except for the TSS, the physiochemical parameters of the groundwater vary with season and are within the permissible limits. The electrical conductivity (EC), turbidity, Phosphorus, Biochemical oxygen demand (BOD), Dissolve oxygen …

Resolving Acne With Optimized Adapalene Microspongeal Gel, In Vivo And Clinical Evaluations, Rania Yehia, Dalia Attia, M. M. Elmazar

Pharmacy

In our pursuit of enhancing acne treatment while minimizing side effects, we developed tailored Adapalene microsponges (MS) optimized using a Box–Behnken design 33. The independent variables, Eudragit RS100 percentage in the polymer mixture, organic phase volume, and drug to polymer percentage, were explored. The optimized formulation exhibited remarkable characteristics, with a 98.3% ± 1.6 production yield, 97.3% ± 1.64 entrapment efficiency, and a particle size of 31.8 ± 1.1 μm. Notably, it achieved a 24 h cumulative drug release of 75.1% ± 1.4. To delve deeper into its efficacy, we evaluated the optimized microspongeal-gel in vitro, in vivo, and clinically. …

The E-Liquid Flavorings Cinnamaldehyde, Vanillin, And Ethyl Vanillin Induce Cellular Stress Responses In Human Proximal Tubule (Hk-2) Epithelial Cells, Ashley J. Cox

Theses, Dissertations and Capstones

The use of electronic nicotine delivery systems (ENDS) has become popular in recent years as an alternative to traditional cigarettes. These devices heat and subsequently vaporize e-liquids for inhalation by the user, which allows for the delivery of ingredients such as flavorings, nicotine, and solvents through the vapor. Flavorings used in e-liquids are “generally recognized as safe” (GRAS) for consumption by the Food and Drug Administration (FDA), however there are currently no recommendations on safety regarding the inhalation of flavoring agents. While research characterizing effects of e-liquids and their flavorings is abundant in lung and respiratory tract models, few studies …

Production Of Vp3-Only Aav2 Vlp In E. Coli, Chengyu Fu

Theses and Dissertations

Adeno-associated virus (AAV) is a widely used vector for gene therapy. However, few studies have focused on producing AAV-based virus-like particles (VLP) in E. coli. This project aimed to express VP3 of AAV2 or co-express VP3 of AAV2 with other proteins, such as E. coli chaperones and/or assembly-activating protein (AAP) in E. coli under different expression conditions and explore the potential to produce VP3-only VLP of AAV2 in situ in E. coli. The constructed plasmid pET15ΔHis-VP3 was used to express VP3 under different conditions. The results demonstrated that most expressed VP3 was in inclusion bodies in all tested conditions. Although …

Mobocertinib Antagonizes Multidrug Resistance In Abcb1- And Abcg2-Overexpressing Cancer Cells, Xingduo Dong

Theses and Dissertations

The resistance of cancer cells to multiple drugs, known as multidrug resistance (MDR), remains a significant obstacle that leads to the ineffectiveness of cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1 and ABCG2, has been strongly correlated with MDR. There is an urgent need to explore and identify novel inhibitors targeting ABCB1 and ABCG2 to overcome the related MDR. Mobocertinib (TAK-788) is an orally administered, irreversible EGFR/HER2 inhibitor approved for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations. This study …

What Influences Trust In And Understanding Of Clinical Trials? An Analysis Of Information And Communication Technology Use And Online Health Behavior From The Health Information National Trends Survey, Aurora Occa, Allison S. Merritt, Allison Leip, Jerod L. Stapleton

UK CARES Faculty Publications

Background: Using information and communication technologies to seek, discuss, and share health-related information influences people’s trust and knowledge of several health practices. However, we know little about the associations between individuals’ information and communication technology use and their perceptions of trust and knowledge of clinical trials. Examining these associations may lead to the identification of target audiences and channels for developing effective educational interventions and campaigns about clinical trials.

Methods: In this study, we analyzed Health Information National Trends Survey data to document perceptions of clinical trial-related knowledge and trust that were recently added as questions in this annual national …

The Effects Of Alcohol On Crash Avoidance Reaction Time In A Driving Simulator Task In Humans, Aishwarya Vasudevan

Wayne State University Theses

AIM 1: Alcohol-impaired driving continues to be a significant cause of car crash injuries and deaths. The blood alcohol concentration (BAC) cut-off level for drunk driving is 0.08% in Michigan, and is estimated that lowering this cut-off to 0.05%would save 500–800 lives every year in the US alone. We used a portable virtual reality (VR)-based driving simulator to demonstrate the effects of alcohol at BAC concentrations 0.02-0.08%, grouped into 0.01% increments, on driving performance, specifically Crash Avoidance Reaction Time (CART), i.e., the time (in msec) required to initiate a steering avoidance response. We found that BAC concentrations as low as …

High-Throughput Screening Of Fda-Approved Drugs For Protecting Retinal Pigment Epithelial Cells Against Er Stress Induced Cell Death: Implications For Age-Related Macular Degeneration, Shaima Ali Jawarneh

Wayne State University Theses

Purpose: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population, characterized by the degeneration of the retinal pigment epithelium (RPE). The link between endoplasmic reticulum (ER) stress and AMD is well established, however FDA-approved medications for the treatment of AMD caused by unregulated ER stress are limited and have potential side effects. The purpose of this study was to conduct a comprehensive screening of the FDA-approved drug library in order to identify potential candidates that could be repurposed in order to protect against the degeneration and death of RPE cells due to ER stress.

Methods: …

Photoluminescence Switching In Quantum Dots Connected With Fluorinated And Hydrogenated Photochromic Molecules, Ephraiem S. Sarabamoun, Jonathan M. Bietsch, Pramod Aryal, Amelia G. Reid, Maurice Curran, Grayson Johnson, Esther H. R. Tsai, Charles W. Machan, Guijun Wang, Joshua J. Choi

Chemistry & Biochemistry Faculty Publications

We investigate switching of photoluminescence (PL) from PbS quantum dots (QDs) crosslinked with two different types of photochromic diarylethene molecules, 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (1H) and 4,4'-(1-perfluorocyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (2F). Our results show that the QDs crosslinked with the hydrogenated molecule (1H) exhibit a greater amount of switching in photoluminescence intensity compared to QDs crosslinked with the fluorinated molecule (2F). With a combination of differential pulse voltammetry and density functional theory, we attribute the different amount of PL switching to the different energy levels between 1H and 2F molecules which result in different potential barrier …

Design Of Kappa Opioid Receptor Agonists For Potential Treatment Of Multiple Sclerosis, Lindsay Kornberger

Theses and Dissertations--Pharmacy

Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system characterized by demyelination and neuroinflammation. There is currently no cure for MS. There is a critically unmet need for the development of pharmacotherapies that can induce remyelination promoting both repair and recovery. The kappa opioid receptor (KOR) has been identified as a potential target for the development of remyelinating pharmacotherapies. KOR activation has been shown to promote functional recovery and remyelination preclinically. However, typical KOR agonists like U50,488 have limitations such as sedation and dysphoria limiting their use. This necessitates further development of new KOR agonists that maintain …

Sensitizing Keap1 Loss Non-Small Cell Lung Cancer To Artesunate Anti-Cancer Activity, Keng Hee Peh

Theses and Dissertations--Pharmacy

Lung cancer is the global leading cause of cancer related death. Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancer diagnoses conferring a significant disease burden. However, certain mutations in tumor suppressors such as Kelch-like ECH-associated protein 1 (KEAP1) confers resistance to standard of care therapy in NSCLC. KEAP1 is known to regulate multiple cellular processes such as oxidative stress response and anti-apoptotic pathways. Furthermore, KEAP1 loss of function in NSCLC is associated with poorer clinical outcomes and there are no currently approved therapies for KEAP1 loss NSCLC and represents an unmet clinical need. Artesunate (Art) demonstrated anti-cancer …

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

Therapeutic Intervention Of Neuroinflammation In Alzheimer Disease By Inhibition Of Classical Complement Pathway Using Anti-C1r Loaded Exosomes, Terjahna Richards

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disease associated with memory decline and cognitive impairment. It is a growing global health and socioeconomic concern, affecting more than 50 million people worldwide. Current therapeutics focus solely on symptomatic management instead of preventative or curative strategies. This is mainly a result of the complexity of the pathophysiological mechanism and the poor understanding of the disease progression. Recently, studies have focused on bridging knowledge gaps giving rise to substantial evidence on the vital role of neuroinflammation in the progression of AD. Neuroinflammation has been shown to be a precursor to apparent amyloid plaque accumulation …

Hjp 272, An Endothelin Receptor Antagonist, And Its Role In Cancer Cell Migration And Invasion, Nabeela Fatima Baig

Theses and Dissertations

Endothelins are a family of versatile peptides composed of 21 amino acids with three isoforms: ET-1, ET-2, and ET-3. As the most abundant of the three isoforms, ET-1 is involved in various biological processes, such as regulation of vascular tone, humoral homeostasis, and neural crest development. However, focus is now being directed towards investigating the functions of the Endothelin axis in the progression of different tumor types including ovarian, prostate, breast, lungs etc. HJP 272 is a novel ETAR antagonist and while our group has previously researched its effects on lung inflammation and preterm birth, this study marks the first …

Characterizing The Role Of Epigenetic Regulator Menin In Pediatric Neuroblastoma Growth Using Pre-Clinical Models, Rameswari Chilamakuri

Theses and Dissertations

Epigenetic regulators such as Menin and MLL1 drive cancer progression, metastasis, and relapse. MLL1 forms a COMPASS complex with its binding partners, including Menin, to function as an epigenetic enzyme H3K4 methyltransferase. H3K4 methyltransferases are known to promote cancer stem cells' (CSCs) self-renewal capacity and metastasis. CSCs are one of the major causes of tumor relapse and metastasis conditions, ultimately leading to poor overall patient survival. Neuroblastoma (NB) is an extracranial solid tumor that accounts for 8-10% of all pediatric cancers, and approximately 50% of patients display metastasis at the time of diagnosis. In this study, we hypothesized and used …

Opioid System's Potential Involvement In Ketamine's Cognitive And Antidepressant-Like Effects In Rats, Fan Zhang

Theses and Dissertations

Depression stands as one of the most pervasive mental health challenges worldwide, including the United States. Conventional antidepressants typically display a delayed onset of therapeutic action (4-8 weeks) and lack efficacy in a substantial portion of patients (over 40% of depressed patients are treatment-resistant). The dissociative anesthetic ketamine, which is a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, has emerged as a promising novel treatment due to its rapid and prolonged antidepressant effects, and it is especially beneficial for treatment-resistant depression. Nevertheless, the precise neurochemical mechanisms underlying ketamine’s antidepressant properties remain elusive, hampering the development of safer and more efficacious treatments. The present …

Examining The Effects Of Artemisia Annua On Neuro2a Cells, Wesley Lim

Honors Undergraduate Theses

Artemisia annua L. is a well-known medicinal herb used in Traditional Chinese Medicine for many centuries and contains artemisinin, which exhibits antimalarial properties [1] and is a potential treatment for SARS-CoV-2 [2]. However, the neurological effect of A. annua and its compounds are poorly understood. We hypothesize that A. annua extracts and artemisinin will provide protection against oxidative stress in mouse neuronal Neuro2A cells. Superoxide dismutase 1 (SOD1) is an anti-oxidant enzyme that protects against oxidative damage [3]. Growth Arrest and DNA Damage-inducible 45 alpha (Gadd45a) is involved in DNA repair and is a common biomarker for DNA damage[4]. SOD1 …

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …

Impacts Of Xylazine On Fentanyl Demand, Body Weight, And Acute Withdrawal In Rats: A Comparison To Lofexidine, Safiyah M. Sadek, Shailesh N. Khatri, Zachary A. Kipp, Kelly E. Dunn, Joshua S. Beckmann, William W. Stoops, Terry D. Hinds, Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl’s behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is …