Search results for "naltrexone"
showing 10 items of 23 documents
The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeki…
2015
Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioi…
‘Not at all what I had expected’: Discontinuing treatment with extended-release naltrexone (XR-NTX): A qualitative study
2021
Background: Extended-release naltrexone (XR-NTX), an opioid antagonist, has demonstrated equal treatment outcomes, in terms of safety, opioid use, and retention, to the recommended OMT medication buprenorphine. However, premature discontinuation of XR-NTX treatment is still common and poorly understood. Research on patient experiences of XR-NTX treatment is limited. We sought to explore participants' experiences with discontinuation of treatment with XR-NTX, particularly motivation for XR-NTX, experiences of initiation and treatment, and rationale for leaving treatment. Methods: We conducted qualitative, semi-structured interviews with participants from a clinical trial of XR-NTX. The study…
Controlled delivery of naltrexone by an intraoral device: in vivo study on human subjects.
2013
Naltrexone is widely used in the treatment of opiate addiction but its current peroral administration is characterized by low bioavailability with various side effects. The development of a long-acting transbuccal delivery device (IntelliDrug) for NLX may be useful to improve patient compliance and the therapy effectiveness. The aims of the study are (a) to test basic safety and effectiveness of controlled transbuccal drug delivery on human subjects; (b) to compare NLX bioavailability following transbuccal delivery vs per os conventional delivery; and (c) to test the hypothesis that transbuccal delivery is more efficient than the conventional route. In this randomized cross-over pilot study…
Diffusion of naltrexone across reconstituted human oral epithelium and histomorphological features
2006
Abstract In transbuccal absorption a major limitation could be the low permeability of the mucosa which implies low drug bioavailability. The ability of naltrexone hydrochloride (NLX) to penetrate a resembling histologically human buccal mucosa was assessed and the occurrence of any histomorphological changes observed. We used reconstituted human oral (RHO) non-keratinised epithelium as mucosal section and a Transwell diffusion cells system as bicompartmental model. Buccal permeation was expressed in terms of drug flux ( J s ) and permeability coefficients ( K p ). Data were collected using both artificial and natural human saliva. The main finding was that RHO does not restrain NLX permeat…
Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: a trial on pigs.
2010
Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction. The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, versus an intravenous (I.V.) bolus of the same drug dose; b) to verify the func…
Release of naltrexone on buccal mucosa: Permeation studies, histological aspects and matrix system design
2007
Transbuccal drug delivery has got several well-known advantages especially with respect to peroral way. Since a major limitation in buccal drug delivery could be the low permeability of the epithelium, the aptitude of NLX to penetrate the mucosal barrier was assessed. Ex vivo permeation across porcine buccal mucosa 800 microm thick was investigated using Franz type diffusion cells and compared with in vitro data previously obtained by reconstituted human oral epithelium 100 microm thick. Both fluxes (Js) and permeability coefficients (K(p)) are in accordance, using either buffer solution simulating saliva or natural human saliva. Permeation was evaluated also in presence of chemical enhance…
Sensitivity of neuronal nicotinic acetylcholine receptors to the opiate antagonists naltrexone and naloxone: receptor blockade and up-regulation
2003
In HEK293 cells stably expressing alpha4beta2 nAChRs, naltrexone, but not naloxone, blocked alpha4beta2 nAChRs via an open-channel blocking mechanism. In primary hippocampal cultures, naltrexone inhibited alpha7 nAChRs up-regulated by nicotine, and in organotypic hippocampal cultures naltrexone caused a time-dependent up-regulation of functional alpha7 nAChRs that was detected after removal of the drug. These results indicate that naltrexone could be used as a smoking cessation aid.
Naltrexone antagonizes acetaldehyde-induced increments in dopamine neurons activity
2014
Abstract Acetaldehyde is the main metabolite of ethanol ingested through alcoholic beverages. Traditionally considered aversive is presently being viewed as an activating agent of the mesolimbic dopamine system but underlying mechanisms are only partially known. Here we show that acetaldehyde-induced increase in firing rate, burst firing and spikes/burst of antidromically-identified ventro-tegmental area Nucleus Accumbens-projecting neurons are abolished by pretreatment with the opiate unselective antagonist naltrexone (1mg/kg/ip). Similar effects are obtained after administration of naloxone (0.1mg/kg/iv). These results indicate: 1) endogenous opiate system(s) participate in acetaldehyde-i…
Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans
2021
Abstract A runner's high describes a sense of well-being during endurance exercise characterized by euphoria and anxiolysis. It has been a widespread belief that the release of endogenous opioids, such as endorphins, underlie a runner's high. However, exercise leads to the release of two classes of rewarding molecules, endocannabinoids (eCBs) and opioids. In mice, we have shown that core features of a runner's high depend on cannabinoid receptors but not opioid receptors. In the present study, we aimed to corroborate in humans that endorphins do not play a significant role in the underlying mechanism of a runner's high. Thus, we investigated whether the development of two core features of a…
Sodium Oxybate Therapy for Alcohol Withdrawal Syndrome and Keeping of Alcohol Abstinence
2018
BACKGROUND Gamma-hydroxybutyrate (GHB or sodium oxybate) is both an exogenous and endogenous molecule with neuromodulator properties. In the United States, GHB is an approved drug for the treatment of narcolepsy and narcolepsy with cataplexy in adults. In some European Union countries, sodium oxybate is applied for the treatment of opioid and alcohol withdrawal. OBJECTIVE The aim of the present review was to describe the state of art of the pre-clinical research and the clinical evidence related to GHB used alone or in combination with other treatments in alcohol withdrawal syndrome and alcohol abstinence maintenance. METHOD Internationally published pre-clinical findings and clinical studi…