Abstract:
:Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the clinical practice. Unfortunately, together with analgesia, a number of adverse effects can occur such as nausea, vomiting, constipation, gastrointestinal alterations and cognitive impairments. Naltrexone is a competitive antagonist of opioid receptors commonly used to treat opioid addiction; its oral use against agonists side effects is limited by the decrease of opioids-therapeutic efficacy and own adverse effects. The intranasal delivery of naltrexone could offer a quick and effective achievement of CNS based on extracellular mechanisms including perineural and perivascular transport. The aim of the study was to test the efficacy of intranasal low-dose naltrexone in reducing intraperitoneal morphine and oxycodone side effects in rodents. In mice, 1 μg naltrexone intranasally administered 30 min before opioids reduced cognitive impairments and motor alteration induced by 10 mg kg-1 morphine and 60 mg kg-1 oxycodone in the Passive avoidance and Rota rod tests, respectively. Moreover, naltrexone rebalanced opioid-induced reduction of the intestinal transit and latency of feces expulsion as well as food intake inhibition. Importantly, 1 μg naltrexone instillation did not block analgesia as demonstrated by the Hot plate test. In rats, intranasal naltrexone counteracted the opioid-induced pica phenomenon related to emesis and increased water and palatable food intake. The effects were comparable to that achieved by metoclopramide used as reference drug. Treatments did not influence body weight. Lastly, the safety of the intranasal delivery has been checked by hematoxylin-eosin staining that did not show histological alterations of the nasal cavity. In conclusion, intranasal low-dose naltrexone counteracted morphine and oxycodone induced gastrointestinal and CNS side effects without impairing opioid analgesia. It is a candidate to be a valid clinical strategy deserving deep analysis.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Micheli L,Di Cesare Mannelli L,Lucarini E,Parisio C,Toti A,Fiorentino B,Rigamonti MA,Calosi L,Ghelardini Cdoi
10.3389/fphar.2020.576624subject
Has Abstractpub_date
2020-09-18 00:00:00pages
576624issn
1663-9812journal_volume
11pub_type
杂志文章abstract::γ-aminobutyric acid (GABA) or glucagon-like peptide-1 based drugs, such as sitagliptin (a dipeptidyl peptidase-4 inhibitor), were shown to induce beta cell regenerative effects in various diabetic mouse models. We propose that their combined administration can bring forth an additive therapeutic effect. We tested this...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00362
更新日期:2017-06-20 00:00:00
abstract::Background: Rhein is considered to have beneficial influence on diabetic nephropathy. Animal experiments suggested that the mechanisms of rhein against diabetic nephropathy may involve many processes, but the credibility of the evidence is unclear. Therefore, we conducted systematic review and meta-analysis of pre-cli...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2019.01473
更新日期:2019-12-13 00:00:00
abstract::The Kinin B2 receptor (B2R) is classically involved in vasodilation and inflammatory responses. However, through the observation of hypoglycemic effects of Angiotensin-I-Converting Enzyme (ACE) inhibitors, this protein has been related to metabolic glucose modulation in physiological and pathophysiological contexts. A...
journal_title:Frontiers in pharmacology
pub_type:
doi:10.3389/fphar.2020.01162
更新日期:2020-08-04 00:00:00
abstract::Oxidative insult, inflammation, apoptosis and autophagy play a pivotal role in the etiology of diabetic nephropathy, a global health concern. Ferulic acid, a phytochemical, is reported to protect against varied diseased conditions. However, the ameliorative role and mechanisms of ferulic acid in averting STZ-mediated ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00027
更新日期:2019-02-05 00:00:00
abstract::Emerging evidence has demonstrated that epigenetic regulation plays a vital role in gene expression under normal and pathological conditions. Alterations in the expression and activation of histone methyltransferases (HMTs) have been reported in preclinical models of multiple kidney diseases, including acute kidney in...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01393
更新日期:2019-12-06 00:00:00
abstract::Enterovirus 71 (EV71) was implicated in a widespread outbreak of hand-foot-and-mouth disease (HFMD) across the Asia Pacific area since 1997 and has also been reported sporadically in patients with brain stem encephalitis. Neurogenic shock with pulmonary edema (PE) is a fatal complication of EV71 infection. Among inotr...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2016.00082
更新日期:2016-03-29 00:00:00
abstract::The market authorization procedure for medicinal products for human use is relying on their demonstrated efficacy, safety, and pharmaceutical quality. This applies to all medicinal products whether of chemical or biological origin. Since October 2009, the first advanced therapy medicinal product (ATMP) has been author...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2012.00012
更新日期:2012-02-14 00:00:00
abstract::Digoxin is widely used to treat heart failure. Epidemiological studies suggested it might be used as an anticancer drug or sensitizing agent for cancer therapy. Adriamycin is a well-known anticancer drug, but often causes cardiotoxicity which limits its use. We recently investigated the anticancer effects of digoxin a...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00186
更新日期:2020-02-28 00:00:00
abstract::The scaffold protein syntenin abounds during fetal life where it is important for developmental movements. In human adulthood, syntenin gain-of-function is increasingly associated with various cancers and poor prognosis. Depending on the cancer model analyzed, syntenin affects various signaling pathways. We previously...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00241
更新日期:2015-10-21 00:00:00
abstract::Type III and IV Bartter syndromes (BS) are rare kidney tubulopathies caused by loss-of-function mutations in the CLCNKB and BSND genes coding respectively for the ClC-Kb chloride channels and accessory subunit barttin. ClC-K channels are expressed in the Henle's loop, distal convoluted tubule, and cortical collecting ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00327
更新日期:2020-03-17 00:00:00
abstract::Radiotherapy and chemotherapy are widespread clinical modalities for cancer treatment. Among other biological influences, hypoxia is a main factor limiting the efficacy of radiotherapy, primarily because oxygen is involved in the stabilization of the DNA damage caused by ionizing radiations. Radiobiological hypoxia is...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2012.00094
更新日期:2012-05-21 00:00:00
abstract::The Glp-1 analog, liraglutide (Lir), has been shown to reduce infarct size and improve cardiac function after myocardial ischemia in rodents with or without diabetes. However, the effect of Lir on angiotensin II (AngII) and pressure overload induced cardiac hypertrophy in nondiabetic mice and the underlying mechanisms...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00537
更新日期:2019-06-05 00:00:00
abstract::Cucurbitacin C (CuC), a novel analogue of triterpenoids cucurbitacins, confers a bitter taste in cucumber. Genes and signaling pathways responsive for biosynthesis of CuC have been identified in the recent years. In the present study, we explored the anti-cancer effects of CuC against human cancers in vitro and in viv...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01287
更新日期:2019-11-08 00:00:00
abstract:INTRODUCTION:European countries need to learn from each other to address unsustainable increases in pharmaceutical expenditures. OBJECTIVE:To assess the influence of the many supply and demand-side initiatives introduced across Europe to enhance prescribing efficiency in ambulatory care. As a result provide future gui...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2010.00141
更新日期:2011-01-07 00:00:00
abstract::Cancer stem cells are involved in cancer establishment, progression, and resistance to current treatments. We demonstrated the in vitro and in vivo anti-breast cancer effect of bakuchiol in a previous study. However, the ability of bakuchiol to target breast cancer stem cells (BCSCs) and inhibit breast cancer metastas...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00746
更新日期:2017-10-18 00:00:00
abstract::[This corrects the article on p. 727 in vol. 8, PMID: 29114222.]. ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,已发布勘误
doi:10.3389/fphar.2017.00964
更新日期:2018-01-09 00:00:00
abstract::Background and Objectives: Limited research focuses on the risk of ischemic cerebrovascular disease associated with use of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) in patients with type 2 diabetes mellitus in Taiwan. This study aimed to investigate the association between DPP-4 inhibitors use and the first...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00859
更新日期:2017-11-22 00:00:00
abstract::BY VIRTUE OF BEING THE PRODUCT OF THE GENETIC ADMIXTURE OF THREE ANCESTRAL ROOTS: Europeans, Africans, and Amerindians, the present-day Brazilian population displays very high levels of genomic diversity, which have important pharmacogenetic/-genomic (PGx) implications. Recognition of this fact has prompted the creati...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2012.00191
更新日期:2012-11-06 00:00:00
abstract::Nanoparticle-based antibiotic constructs have become a popular area of investigation in the biomedical sciences. Much of this work has pertained to human diseases, largely in the cancer therapy arena. However, considerable research has also been devoted to the nanochemistry for controlling infectious diseases. Among t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.01121
更新日期:2019-10-04 00:00:00
abstract::In glaucoma, studies revealed an involvement of the complement system. In an experimental autoimmune glaucoma model, immunization with an optic nerve homogenate antigen (ONA) led to retinal ganglion cell (RGC) loss, while intraocular pressure (IOP) remained unchanged. Here, we investigated the therapeutic effect of a ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01381
更新日期:2019-12-02 00:00:00
abstract:RATIONALE:Alzheimer's disease (AD) is a debilitating disease with complex pathophysiology. Amyloid beta (Aβ) (1-42) is a reliable model of AD that recapitulates many aspects of human AD. OBJECTIVE:The intent of the present study was to investigate the neuroprotective potential of Coenzyme Q10 (CoQ10) and its modulatio...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00268
更新日期:2015-11-09 00:00:00
abstract::Over the past several decades, natural products with poly-pharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Berberine (PubChem CID: 2353), a soliloquies quaternary alkaloid, has been validated to exert powerful effects in many cancers. However, the...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00857
更新日期:2019-08-06 00:00:00
abstract::Several reports have shown that the periventricular region of the brain, including the paraventricular nucleus (PVN), is critical to sensing and responding to changes in plasma osmolality. Further studies also implicate the transient receptor potential ion channel, type V4 (TRPV4) channel in this homeostatic behavior....
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00083
更新日期:2015-04-23 00:00:00
abstract::The aim of this study was to investigate the regulatory function of the non-coding microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in alcoholic hepatitis (AH) and its potential mechanism associated with the mitogen-activated protein kinase (MAPK) signaling pathway. Levels of alanine aminotransfer...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00270
更新日期:2020-04-07 00:00:00
abstract::The entactogen MDMA (3,4-methylenedioxy-methamphetamine, "Ecstasy") exerts its psychotropic effects acting primarily as a substrate of the serotonin transporter (SERT) to induce a non-exocytotic release of serotonin. Nevertheless, the roles of specific positions of the aromatic ring of MDMA associated with the modulat...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00157
更新日期:2019-02-28 00:00:00
abstract::The need for novel drugs for the treatment of autoimmune diseases is high, since available pharmaceuticals often have substantial side effects and limited efficacy. Natural products are a good starting point in the development of immunosuppressive leads. Since enhanced T cell proliferation is a common feature of autoi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00402
更新日期:2020-04-08 00:00:00
abstract::Cerebral energy deficiency is a key pathophysiologic cascade that results in neuronal injury and necrosis after ischemic stroke. Shengui Sansheng San (SSS) has been used to treat stroke for more than 300 years. In present study, we investigated the therapeutic efficacy and mechanism of SSS extraction on cerebral energ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00386
更新日期:2019-04-23 00:00:00
abstract::There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2016.00422
更新日期:2016-11-08 00:00:00
abstract:Background:Pancreatic cancer is one of the most aggressive malignancies. Bufalin, a traditional Chinese medicine, has been used to treat pancreatic cancer as an antitumor agent although the mechanism by which it exerts its effects is still unclear. c-Myc has been found to be overexpressed in more than half of human can...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00495
更新日期:2020-04-17 00:00:00
abstract::Since the clinical use of digitalis as the first pharmacological therapy for atrial fibrillation (AF) 235 years ago in 1785, antiarrhythmic drug therapy has advanced considerably and become a cornerstone of AF clinical management. Yet, a preventive or curative panacea for sustained AF does not exist despite the rise o...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.581837
更新日期:2020-11-09 00:00:00