The poor aqueous solubility of 2-arachidonyl glyceryl ether (noladin ether) 2 hinders both pharmacological studies and pharmaceutical development. The synthesized mono- and diphosphate esters of noladin ether (4 and 6) considerably increased the aqueous solubility of noladin ether (>40000-fold), showed high stability against chemical hydrolysis in buffer solutions, and were rapidly converted to the parent drug via enzymatic hydrolysis. The monophosphate ester of noladin ether reduced intraocular pressure in normotensive rabbits.

Download full-text PDF

Source
http://dx.doi.org/10.1021/jm030877jDOI Listing

Publication Analysis

Top Keywords

noladin ether
20
intraocular pressure
8
aqueous solubility
8
ether
6
noladin
5
synthesis vitro
4
vitro evaluation
4
evaluation intraocular
4
pressure effects
4
effects water-soluble
4

Similar Publications

Background: Central sensitization has been widely accepted as an underlying pathophysiological mechanism of chronic migraine (CM), activation of cannabinoid type-1 receptor (CB1R) exerts antinociceptive effects by relieving central sensitization in many pain models. However, the role of CB1R in the central sensitization of CM is still unclear.

Methods: A CM model was established by infusing inflammatory soup (IS) into the dura of male Wistar rats for 7 days, and hyperalgesia was assessed by the mechanical and thermal thresholds.

View Article and Find Full Text PDF

Three of a Kind: Control of the Expression of Liver-Expressed Antimicrobial Peptide 2 (LEAP2) by the Endocannabinoidome and the Gut Microbiome.

Molecules

December 2021

Quebec Heart and Lung Institute Research Centre, Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada.

The endocannabinoidome (expanded endocannabinoid system, eCBome)-gut microbiome (mBIome) axis plays a fundamental role in the control of energy intake and processing. The liver-expressed antimicrobial peptide 2 (LEAP2) is a recently identified molecule acting as an antagonist of the ghrelin receptor and hence a potential effector of energy metabolism, also at the level of the gastrointestinal system. Here we investigated the role of the eCBome-gut mBIome axis in the control of the expression of LEAP2 in the liver and, particularly, the intestine.

View Article and Find Full Text PDF

A simple LC-MS/MS method for the simultaneous quantification of endocannabinoids in biological samples.

J Chromatogr B Analyt Technol Biomed Life Sci

December 2020

Institute of Pharmacology and Toxicology, Rostock University Medical Center, Rostock, Germany. Electronic address:

The arachidonic acid derivatives N-arachidonoylethanolamine (anandamide; AEA), 2-arachidonoylglycerol (2-AG), N-arachidonoyldopamine (NADA), 2-arachidonoylglycerol ether (noladin ether; 2-AGE) and O-arachidonoylethanolamine (virodhamine; VA) were identified as physiological components of the endocannabinoid (EC) system. In order to gain further profound knowledge about the different EC-induced physiological and pathophysiological effects, appropriate analytical methods are required. The method described here uses liquid chromatography in combination with positive electrospray ionization mass spectrometry (LC-MS/MS) to quantify the concentrations of the above-mentioned EC compounds in cells.

View Article and Find Full Text PDF

Endocannabinoids and endocannabinoid-like compounds modulate hypoxia-induced permeability in CaCo-2 cells via CB, TRPV1, and PPARα.

Biochem Pharmacol

October 2019

Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, Royal Derby Hospital, University of Nottingham, Nottingham, UK. Electronic address:

Background And Purpose: We have previously reported that endocannabinoids modulate permeability in Caco-2 cells under inflammatory conditions and hypothesised in the present study that endocannabinoids could also modulate permeability in ischemia/reperfusion.

Experimental Approach: Caco-2 cells were grown on cell culture inserts to confluence. Trans-epithelial electrical resistance (TEER) was used to measure permeability.

View Article and Find Full Text PDF

Interactions of endocannabinoid virodhamine and related analogs with human monoamine oxidase-A and -B.

Biochem Pharmacol

September 2018

Department of BioMolecular Sciences and National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, United States; National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, United States. Electronic address:

The endocannabinoid system plays an important role in the pathophysiology of various neurological disorders, such as anxiety, depression, neurodegenerative diseases, and schizophrenia; however, little information is available on the coupling of the endocannabinoid system with the monoaminergic systems in the brain. In the present study, we tested four endocannabinoids and two anandamide analogs for inhibition of recombinant human MAO-A and -B (monoamine oxidase). Virodhamine inhibited both MAO-A and -B (IC values of 38.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!