Stereoselective modulatory actions of oleamide on GABAA receptors and voltage‐gated Na+ channels in vitro: a putative endogenous ligand for depressant drug sites in CNS

Verdon, Bernard; Zheng, Jian; Nicholson, Russell A.; Ganelli, C Robin; Lees, George

doi:10.1038/sj.bjp.0703051

Cited by 49 publications

(26 citation statements)

References 35 publications

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“…It exhibits cannabinoid-like behavioral responses without binding significantly to CB receptors (Ki = 1.14µM for CB1) [104][105][106]. ODA behaves as a full agonist at rat and human CB1 receptors [106] and has been found to modulate serotonin receptors [104,[107][108][109][110], benzodiazepine-sensitive GABA A receptors [111,112], and antagonize glial gap junction cell communication [113,114]. Its physiological role remains to be fully elucidated.…”

Section: Hybrid Cannabinoidsmentioning

confidence: 99%

CB1 Cannabinoid Receptor Ligands

Thakur¹,

Nikas²,

Makriyannis³

2005

MRMC

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The CB1 receptor is expressed in the central nervous system and numerous other tissues including heart, lung and uterus and has been recognized as an important therapeutic target for pain, appetite modulation, glaucoma, multiple sclerosis and other indications. An interesting feature of this GPCR is its ability to be activated by a number of structurally different classes of compounds, thus, raising the possibility of multiple activated forms of the receptor. Understanding of the structure-activity relationships of cannabinergic ligands has paved the road for the development of novel ligands exhibiting receptor subtype selectivity and efficacy. This review highlights the important CB1 cannabinergic ligands developed to date.

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Section: Hybrid Cannabinoidsmentioning

confidence: 99%

CB1 Cannabinoid Receptor Ligands

Thakur¹,

Nikas²,

Makriyannis³

2005

MRMC

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“…N-Arachidonoyldopamine CB 1 , TRPV1, and non-CB 1 /CB 2 GPCR (in the aorta) [38,39,41] N-Oleoyldopamine PPARα, PPARγ, and TRPV1 [38,39] C. [120][121][122] a In some cases, the indicated fatty acid amide has not been demonstrated to bind to the listed target by direct binding, but instead has been shown to be an agonist or antagonist to the target using a reporter assay. For exact details, the reader is pointed to the cited references.…”

Section: A N-acylethanolaminesmentioning

confidence: 99%

Biosynthesis, degradation and pharmacological importance of the fatty acid amides

Farrell

Merkler

2008

Drug Discovery Today

111

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The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologically-occurring fatty acid amides. In this review, we will outline which fatty acid amides have been isolated from mammalian sources, detail what is known about how these molecules are made and degraded in vivo, and highlight their potential for the development of novel therapeutics. Keywords N-acylamino acid; N-acyldopamine; N-acylethanolamine; primary fatty acid amide; N-acylamideThe fatty acid amide bond has long been recognized in nature, being important in the structure of the ceramides [1] and the sphingolipids [2]. The first non-sphingosine based fatty acid amide isolated from a natural source was N-palmitoylethanolamine from egg yolk in 1957 [3]. Interest in the N-acylethanolamines (NAEs) dramatically increased upon the identification of Narachidonoylethanolamine (anandamide) as the endogenous ligand for the cannabinoid receptors in the mammalian brain [4]. It is now known that a family of NAEs is found in the brain and in other tissues [5,6].In addition to the NAEs, other classes of fatty acid amides have been characterized, namely the N-acylamino acids (NAAs) [7], the N-acyldopamines (NADAs) [8] and the primary fatty acid amides (PFAMs) [9,10] (Figure 1). Relative to NAEs, much less is currently known about the NAAs, the NADAs and the PFAMs, except that they are found in biological systems. The goal of this review is to summarize the current state of knowledge regarding the different classes of endogenous fatty acid amides and highlight their potential for drug discovery (see refs. [11-13] for earlier reviews) © 2008 Elsevier Ltd. All rights reserved.Corresponding author: Merkler, D.J (E-mail: merkler@cas.usf.edu) phone 813-974-3579; fax 813-974-1733. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Teaser SentenceFatty acid amides are a family of mammalian bioactive compounds. These molecules and the enzymes involved in their metabolism provide an opportunity to develop new drugs to treat human disease. -palmitoyl-, N-stearoyl-and N-oleoylethanolamine [5,11], each compromising ≥25% of total brain NAEs. Other less abundant NAEs found in the brain are anandamide, N-linoleoyl-, N-linolenoyl-, N-dihomo-γ-linolenoyl-and N-docosatetraenoylethanolamine [11]. In addition to the brain, the NAEs are widespread in the peripheral tissues [5]. The mos...

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“…Oleamide has unique pharmacological properties and modulates activity of three important signal systems: neuroreceptors (positive modulation of GABA-A receptors and inhibitory glycine receptors [6]), voltage-dependent Na + channels (blockade of function [14]), and gap junction-mediated communication between glial cells (selective inhibition of communication [5]). These systems mediate the effect of antiepileptic compounds.…”

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confidence: 99%