Read by QxMD icon Read

Partial agonist

(no author information available yet)
No single analgesic provides effective pain relief in all patients and increasing the dose of an analgesic may increase its unwanted effects.1 In addition, pain frequently results from multiple mechanisms that may respond to different pharmacological interventions.2 One suggested approach is to combine analgesics with different modes of action, with the aim of delivering better analgesia using lower doses of each drug.1 Skudexa (A. Menarini Farmaceutica Internazionale SRL), a combination of tramadol hydrochloride (a synthetic opioid analgesic that is a partial agonist at the μ, δ and κ opioid receptors) and dexketoprofen (a NSAID), is licensed for short term treatment of moderate to severe acute pain in adults...
June 2018: Drug and Therapeutics Bulletin
Rossella De Marco, Andrea Bedini, Santi Mario Spampinato, Lorenzo Comellini, Junwei Zhao, Roberto Artali, Luca Gentilucci
Herein we present the expedient synthesis of endomorphin-1 analogues containing stereoisomeric β2 -homo-Freidinger lactam-like scaffolds ([Amo2 ]EM), and we discuss opioid receptor (OR) affinity, enzymatic stability, functional activity, in vivo antinociceptive effects, and conformational and molecular docking analysis. Hence, H-Tyr-Amo-Trp-PheNH2 resulted to be a new chemotype of highly stable, selective, partial KOR agonist inducing analgesia, therefore displaying great potential interest as a painkiller possibly with reduced harmful side effects...
June 14, 2018: Journal of Medicinal Chemistry
Mei Yuan, Mei-Na Ma, Ting-Yu Wang, Yan Feng, Pei Chen, Chao He, Sijie Liu, Yun-Xia Guo, Yue Wang, Yao Fan, Lu-Qi Wang, Xiao-Qiang E, Guo-Fen Qiao, Bai-Yan Li
AIM: Substance P (SP) causes vasodilation and blood pressure (BP) reduction. However, the involvement of tachykinin receptors (NKRs) within baroreflex afferent pathway in SP-mediated BP regulation is largely unknown. METHODS: Under control and hypertensive condition, NKRs' expressions were evaluated in nodose (NG) and nucleus of tractus solitary (NTS) of male, female, and ovariectomized (OVX) rats; BP was recorded after microinjection of SP and NKRs agonists into NG; Baroreceptor sensitivity (BRS) was tested as well...
June 13, 2018: CNS Neuroscience & Therapeutics
Juan Carlos González-Orozco, Valeria Hansberg-Pastor, Paulina Valadez-Cosmes, Walter Nicolas-Ortega, Yenifer Bastida-Beristain, Marisol De La Fuente-Granada, Aliesha González-Arenas, Ignacio Camacho-Arroyo
BACKGROUND AND AIMS: Glioblastoma is the most frequent and aggressive brain tumor due to its high capacity to migrate and invade normal brain tissue. The steroid hormone progesterone (P4) contributes to the progression of glioblastoma by promoting proliferation, migration, and cellular invasion through the activation of its intracellular receptor (PR). However, the use of PR antagonist RU486 partially blocks the effects of P4, suggesting the participation of signaling pathways such as those mediated by membrane receptors to P4 (mPRs)...
June 9, 2018: Molecular and Cellular Endocrinology
Yan Yuan, Yajing Zhang, Shiwen Zhao, Jie Chen, Jinlong Yang, Tao Wang, Hui Zou, Yi Wang, Jianhong Gu, Xuezhong Liu, Jianchun Bian, Zongping Liu
Cadmium (Cd) is a toxic metal capable of damaging brain. Studies have demonstrated that Cd can induce apoptosis in neuronal cells. The CD95/APO-1 (Fas)/Fas Ligand (FasL) signaling pathway is one of the primary apoptosis pathways, but the role and regulatory mechanism of this pathway in neuronal cells remain unclear. Here, we demonstrated the underlying mechanism of the Fas/FasL system involving the mitochondrial apoptotic pathway in neuronal cells. Primary rat cerebral cortical neurons and PC12 cells were exposed to Cd, which significantly activated expression of Fas, FasL, Fas-associated death domain (FADD) and cleaved caspase-8...
June 11, 2018: Scientific Reports
Nan Gao, Rao Me, Chenyang Dai, Berhane Seyoum, Fu-Shin X Yu
Pseudomonas aeruginosa keratitis is characterized by severe corneal ulceration and may lead to blindness if not treated properly in a timely manner. Although the roles of the IL-1 subfamily of cytokines are well established, as a newly discovered subfamily, IL-36 cytokine regulation, immunological relevance, and relation with IL-1 cytokines in host defense remain largely unknown. In this study, we showed that P. aeruginosa infection induces the expression of IL-36α and IL-36γ, as well as IL-1β and secreted IL-1Ra (sIL-1Ra), but not IL-36Ra...
June 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Andrei A Yarushkin, Mark E Mazin, Anastasia Y Yunusova, Kseniya V Korchagina, Yuliya A Pustylnyak, Elena A Prokopyeva, Vladimir O Pustylnyak
It was shown that CAR participates in the regulation of many cell processes. Thus, the activation of CAR causes a proliferating effect in the liver, which provides grounds to consider CAR as a therapeutic target when having a partial resection of this organ. Even though a lot of work has been done on the function of CAR in regulating hepatocyte proliferation, very little has been done on its complex mediating mechanism. This study, therefore, showed that the liver growth resulting from CAR activation leads to the decline in the level of PTEN protein and subsequent Akt activation in mouse liver...
June 8, 2018: Biochemical and Biophysical Research Communications
Bharat Bhushan, John W Stoops, Wendy M Mars, Anne Orr, William C Bowen, Shirish Paranjpe, George K Michalopoulos
TCPOBOP (1,4-Bis [2-(3,5-Dichloropyridyloxy)] benzene) is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss. TCPOBOP-induced direct hyperplasia has been considered to be CAR-dependent with no evidence of involvement of cytokines or growth factor signaling. Receptor tyrosine kinases (RTKs), MET and EGFR, are known to play a critical role in liver regeneration after partial hepatectomy, but their role in TCPOBOP-induced direct hyperplasia, not yet explored, is investigated in the current study...
June 11, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Lin Li, Debo Yun, Yuan Zhang, Yihao Tao, Qiang Tan, Fei Qiao, Bo Luo, Yi Liu, Runjin Fan, Jishu Xian, Anyong Yu
BACKGROUND AND PURPOSE: The blood-brain barrier (BBB) disruption and the following development of brain edema, is the most life-threatening secondary injury after intracerebral hemorrhage (ICH). This study is to investigate a potential role and mechanism of JWH133, a selected cannabinoid receptor type2 (CB2R) agonist, on protecting blood-brain barrier integrity after ICH. METHODS: 192 adult male Sprague-Dawley (SD) rats were randomly divided into Sham; ICH+Vehicle; ICH+JWH 1...
June 7, 2018: Brain Research
Jorge M Zuniga, Katsavelis Dimitrios, Jean L Peck, Rakesh Srivastava, James E Pierce, Drew R Dudley, David A Salazar, Keaton J Young, Brian A Knarr
BACKGROUND: Co-contraction is the simultaneous activation of agonist and antagonist muscles that produces forces around a joint. It is unknown if the use of a wrist-driven 3D printed transitional prostheses has any influence on the neuromuscular motor control strategies of the affected hand of children with unilateral upper-limb reduction deficiencies. Thus, the purpose of the current investigation was to examine the coactivation index (CI) of children with congenital upper-limb reduction deficiencies before and after 6 months of using a wrist-driven 3D printed partial hand prosthesis...
June 8, 2018: Journal of Neuroengineering and Rehabilitation
Yixi Zhang, Xiaoyong Xu, Haibo Bao, Xusheng Shao, Zhong Li, Zewen Liu
BACKGROUND: Neonicotinoids, such as imidacloprid, are selective agonists of insect nicotinic acetylcholine receptors (nAChRs) to control Nilaparvata lugens, a major rice insect pest. High imidacloprid resistance has been reported in N. lugens in laboratory and in fields. Cycloxaprid, an oxabridged cis-nitromethylene neonicotinoid, showed high insecticidal activity against N. lugens and low cross-resistance in the imidacloprid resistant strains and field populations. RESULTS: Binding studies have demonstrated that imidacloprid had two binding sites with different affinities (Kd = 3...
June 6, 2018: Pest Management Science
Xiao-Dong Zhuang, Xin He, Da-Ya Yang, Yue Guo, Jian-Gui He, Hai-Peng Xiao, Xin-Xue Liao
BACKGROUND: Cardiovascular (CV) safety of one anti-diabetic medication over another remains partially delineated. We sought to assess the comparative effect on CV outcomes among novel anti-diabetic agents. METHODS: This study was registered with the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched between Jan 1, 1980, and June 30, 2016. Randomized controlled trials comparing anti-diabetic drugs with other comparators in adults with type 2 diabetes were included...
June 5, 2018: Cardiovascular Diabetology
Aniruddha Basu, Jayant Mahadevan, Dhruva Ithal, Sowmya Selvaraj, Prabhat Kumar Chand, Pratima Murthy
Tapentadol is a centrally acting opioid analgesic which has partial opioid agonistic and norepinephrine reuptake inhibitor action similar to its nearest congener and tramadol though with a relatively higher μ-affinity. It has abuse potential, is a scheduled drug, yet currently is not known to be an opioid widely misused in India. However, under the current drug abuse legislation in India, where common prescription opioids such as dextropropoxyphene have been banned, tapentadol may take the center stage of pharmaceutical opioid abuse in the near future...
January 2018: Indian Journal of Pharmacology
K V Derkach, I B Sukhov, V M Bondareva, A O Shpakov
Metformin (MF), a first-line drug in the treatment of diabetes mellitus, has been used in the recent years to treat obesity. Its therapeutic effect is due not only to the influence on the peripheral tissues, but also on the hypothalamus, which controls food behavior and energy metabolism. The aim was to study the effect of MF therapy (200 mg/kg/day, 8 weeks) in rats with obesity caused by a high-carbohydrate/high-fat diet on the metabolic and hormonal parameters and functional state of the hypothalamic signaling systems...
2018: Advances in Gerontology, Uspekhi Gerontologii
Deniz Bagdas, Yasmin Alkhlaif, Asti Jackson, F Ivy Carroll, Joseph W Ditre, M Imad Damaj
Varenicline, a partial agonist for α4β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist for α3β4 and α7 nAChRs, is approved for smoking cessation treatment. Although, partial agonism at α4β2* nAChRs is believed to be the mechanism underlying the effects of varenicline on nicotine reward, the contribution of other nicotinic subtypes to varenicline's effects on nicotine reward is currently unknown. Therefore, we examined the role of α5 and α7 nAChR subunits in the effects of varenicline on nicotine reward using the conditioned place preference (CPP) test in mice...
May 21, 2018: Neuropharmacology
Marisa Briones, Steven Shoptaw, Ryan Cook, Matthew Worley, Aimee-Noelle Swanson, David E Moody, Wenfang B Fang, John Tsuang, Benjamin Furst, Keith Heinzerling
BACKGROUND: Previous studies have suggested that varenicline, an α4β2 nicotinic receptor partial agonist, and α7 nicotinic receptor full agonist, may be effective for the treatment of methamphetamine (MA) dependence due to dopaminergic effects, relief of glutamatergic and cognitive dysfunction, and activation of nicotinic cholinergic systems. This study aimed to determine if varenicline (1 mg BID) resulted in reduced methamphetamine use compared to placebo among treatment-seeking MA-dependent volunteers...
May 25, 2018: Drug and Alcohol Dependence
Sudhakar R Subramaniam, Iddo Magen, Nicholas Bove, Chunni Zhu, Vincent Lemesre, Garima Dutta, Chris Jean Elias, Henry A Lester, Marie-Francoise Chesselet
In addition to dopaminergic and motor deficits, patients with Parkinson's disease (PD) suffer from non-motor symptoms, including early cognitive and social impairment, that do not respond well to dopaminergic therapy. Cholinergic deficits may contribute to these problems, but cholinesterase inhibitors have limited efficacy. Mice over-expressing α-synuclein, a protein critically associated with PD, show deficits in cognitive and social interaction tests, as well as a decrease in cortical acetylcholine. We have evaluated the effects of chronic administration of nicotine in mice over-expressing wild type human α-synuclein under the Thy1-promoter (Thy1-aSyn mice)...
May 31, 2018: Neurobiology of Disease
Lulu Ma, Min Gao, Lin Wu, Xiufen Zhao, Huijuan Mao, Changying Xing
Fibroblastic growth factor 23 (FGF23) is a hormone secreted primarily by bone. FGF23 is elevated in the serum of chronic kidney disease (CKD) patients, but the exact mechanism is not well known. Klotho is identified as an aging suppressor, which is mainly expressed in the kidney, and the level of soluble Klotho is negatively associated with FGF23 in CKD. The aim of this study was to investigate the effect and possible mechanism of Klotho on FGF23 synthesis in osteoblast-like UMR-106 cells. UMR-106 cells were divided into five groups: (1) control group; (2) β-glycerophosphate (β-GP) group; (3) β-GP + Klotho group; (4) β-GP+ lithium chloride (LiCl, a Wnt/β-catenin pathway agonist) group; and (5) β-GP + Klotho + LiCl group...
May 30, 2018: Cell Biology International
Lejla Medzikovic, Cindy van Roomen, Antonius Baartscheer, Pieter B van Loenen, Judith de Vos, Erik N T P Bakker, Duco S Koenis, Amin Damanafshan, Esther E Creemers, E Karin Arkenbout, Carlie J M de Vries, Vivian de Waard
Aims: Cardiac remodelling and heart failure are promoted by persistent sympathetic activity. We recently reported that nuclear receptor Nur77 may protect against sympathetic agonist-induced cardiac remodelling in mice. The sympathetic co-transmitter Neuropeptide Y (NPY) is co-released with catecholamines and is a known cardiac modulator and predictor of heart failure mortality. Recently, transcriptome analyses revealed NPY as a putative target of Nur77. In this study, we assess whether Nur77 modulates adverse cardiac remodelling via NPY signalling...
May 30, 2018: Cardiovascular Research
Ya-Qin Huang, Shao-Hui Guo, Renyu Liu, Sheng-Mei Zhu, Jian-Liang Sun, Yong-Xing Yao
Background: It is known that dexmedetomidine can reduce opioid requirements and that there is a synergistic effect when dexmedetomidine and morphine (a full mu opioid receptor agonist) are administered together. However, it was unclear whether a synergistic or additive effect would be observed when dexmedetomidine was co-administered with a partial mu opioid receptor agonist. The present study was designed to elucidate such effects by intrathecally co-administering dexmedetomidine and dezocine, a partial mu receptor agonist, in a mouse pain model...
May 11, 2018: Oncotarget
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"