http://www.cnr.it/ontology/cnr/individuo/prodotto/ID168640

New N-arachidonoylserotonin analogues with potential 'dual' mechanism of action against pain. (Articolo in rivista)

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Label

New N-arachidonoylserotonin analogues with potential 'dual' mechanism of action against pain. (Articolo in rivista) (literal)

Anno

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Alternative label

Ortar G., Cascio M.G., De Petrocellis L., Morera E. , Rossi F., Schiano-Moriello A., Nalli M., de Novellis V., Woodward D., Maione S., Di Marzo V. (2007)
New N-arachidonoylserotonin analogues with potential 'dual' mechanism of action against pain.
in Journal of medicinal chemistry; ACS, American chemical society, Washington, DC (Stati Uniti d'America)
(literal)

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Ortar G., Cascio M.G., De Petrocellis L., Morera E. , Rossi F., Schiano-Moriello A., Nalli M., de Novellis V., Woodward D., Maione S., Di Marzo V. (literal)

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Note

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1. CNR, Inst Biomol Chem, I-80078 Naples, Italy 2. Univ Roma La Sapienza, Dipartimento Studi Farmaceut, I-00185 Rome, Italy 3. CNR, Inst Cybernet, Endocannabinoid Res Grp, I-80078 Naples, Italy 4. Allergsn Inc, Dept Biol Sci, Irvine, CA 92612 USA 5. Univ Naples 2, Dept Expt Med, Sect Pharmacol L Donatelli, Naples, Italy (literal)

Titolo

New N-arachidonoylserotonin analogues with potential 'dual' mechanism of action against pain. (literal)

Abstract

N-arachidonoylserotonin (AA-5-HT, 1a) is an inhibitor of fatty acid amide hydrolase (FAAH) that acts also as an antagonist of transient receptor potential vanilloid-type 1 (TRPV1) channels and is analgesic in rodents. We modified the chemical structure of 1a with the aim of developing \"hybrid\" FAAH/TRPV1 blockers more potent than the parent compound or obtaining analogues with single activity at either of the two targets to study the mechanism of the analgesic action of 1a. Thirty-eight AA-5-HT analogues, containing a serotonin \"head\" bound to a variety of lipophilic moieties via amide, urea, or carbamate functionalities, were synthesized. Unlike 1a, most of the new compounds possessed activity at only one of the two considered targets. The amides 1b and 1c of alpha- and gamma-linolenic acid, however, showed \"hybrid\" activity similar to 1a. The carbamate 3f (OMDM106), although unable to antagonize TRPV1 receptors, was the most potent FAAH inhibitor in this study (IC50=0.5 microM). Compounds 3f and 1m (OMDM129), which exhibited activity at only FAAH or TRPV1, respectively, were 10-fold less potent than 1a at preventing formalin-induced hyperalgesia in mice. (literal)

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