http://www.cnr.it/ontology/cnr/individuo/prodotto/ID19052

Development of the first ultra-potent \"capsaicinoid\" agonist at transient receptor potential vanilloid type 1 (TRPV1) channels and its therapeutic potential (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Development of the first ultra-potent \"capsaicinoid\" agonist at transient receptor potential vanilloid type 1 (TRPV1) channels and its therapeutic potential (Articolo in rivista) (literal)

Anno

2005-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1124/jpet.104.074864 (literal)

Alternative label

Appendino G., De Petrocellis L., Trevisani M., Minassi A., Daddario N., Schiano Moriello A., Gazzieri D., Ligresti A., Campi B., Fontana G., Pinna C., Geppetti P., Di Marzo V. (2005)
Development of the first ultra-potent "capsaicinoid" agonist at transient receptor potential vanilloid type 1 (TRPV1) channels and its therapeutic potential
in The Journal of pharmacology and experimental therapeutics (Print); American Society Of Pharmacology And Experimental Therapeutics, Bethesda (Stati Uniti d'America)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Appendino G., De Petrocellis L., Trevisani M., Minassi A., Daddario N., Schiano Moriello A., Gazzieri D., Ligresti A., Campi B., Fontana G., Pinna C., Geppetti P., Di Marzo V. (literal)

Pagina inizio

561 (literal)

Pagina fine

570 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

312 (literal)

Rivista

?The ?Journal of pharmacology and experimental therapeutics (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

2 (literal)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

1. CNR, Inst Biomol Chem, Endocannabinoid Res Grp, I-80078 Pozzuoli, NA, Italy 2. Dipartimento Sci Chim Alimentari Farmaceut & Farm, Novara, Italy 3. CNR, Ist Cibernet Eduardo Caianiello, Endocannabinoid Res Grp, I-80078 Pozzuoli, NA, Italy 4. Univ Ferrara, Pharmacol Unit, Dept Clin & Expt Med, I-44100 Ferrara, Italy 5. Indena Ric SpA, Milan, Italy 6. Univ Milan, Dipartimento Sci Farmacol, Milan, Italy 7. Univ Florence, Clin Pharmacol Unit, Dept Crit Care Med & Surg, Florence, Italy (literal)

Titolo

Development of the first ultra-potent \"capsaicinoid\" agonist at transient receptor potential vanilloid type 1 (TRPV1) channels and its therapeutic potential (literal)

Abstract

Olvanil (N-9-Z-octadecenoyl-vanillamide) is an agonist of transient receptor potential vanilloid type 1 (TRPV1) channels that lack the pungency of capsaicin and was developed as an oral analgesic. Vanillamides are unmatched in terms of structural simplicity, straightforward synthesis, and safety compared with the more powerful TRPV1 agonists, like the structurally complex phorboid compound resiniferatoxin. We have modified the fatty acyl chain of olvanil to obtain ultra-potent analogs. The insertion of a hydroxyl group at C-12 yielded a compound named rinvanil, after ricinoleic acid, significantly less potent than olvanil (EC(50) = 6 versus 0.7 nM), but more versatile in terms of structural modifications because of the presence of an additional functional group. Acetylation and phenylacetylation of rinvanil re-established and dramatically enhanced, respectively, its potency at hTRPV1. With a two-digit picomolar EC(50) (90 pM), phenylacetylrinvanil (PhAR, IDN5890) is the most potent vanillamide ever described with potency comparable with that of resiniferatoxin (EC(50), 11 pM). Benzoyl- and phenylpropionylrinvanil were as potent and less potent than PhAR, respectively, whereas configurational inversion to ent-PhAR and cyclopropanation (but not hydrogenation or epoxidation) of the double bond were tolerated. Finally, iodination of the aromatic hydroxyl caused a dramatic switch in functional activity, generating compounds that behaved as TRPV1 antagonists rather than agonists. Since the potency of PhAR was maintained in rat dorsal root ganglion neurons and, particularly, in the rat urinary bladder, this compound was investigated in an in vivo rat model of urinary incontinence and proved as effective as resiniferatoxin at reducing bladder detrusor overactivity. (literal)

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