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Titolo:
Opioid peptide receptor studies. 15. Relative efficacy of 4-[(N-allyl-3-methyl-4 piperidinyl) phenylamino]-N,N-diethylbenzamide and related compoundsat the cloned human delta-opioid receptor
Autore:
Xu, H; Lu, YF; Thomas, JB; Carroll, FI; Rice, KC; Rothman, RB;
Indirizzi:
NIDA, CPS, IRP, DIR,NIH, Baltimore, MD 21224 USA NIDA Baltimore MD USA 21224 A, CPS, IRP, DIR,NIH, Baltimore, MD 21224 USA Res Triangle Inst, Res Triangle Pk, NC 27709 USA Res Triangle Inst Res Triangle Pk NC USA 27709 Triangle Pk, NC 27709 USA NIDDK, LMC, NIH, Bethesda, MD USA NIDDK Bethesda MD USANIDDK, LMC, NIH, Bethesda, MD USA
Titolo Testata:
SYNAPSE
fascicolo: 4, volume: 40, anno: 2001,
pagine: 269 - 274
SICI:
0887-4476(20010615)40:4<269:OPRS1R>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
SELECTIVE LIGANDS; AGONIST EFFICACY; BINDING-SITES; INHIBITION; BIOASSAY; TAN-67; BRAIN; DRUGS;
Keywords:
opioid receptors; analgesics; [S-35]GTP-gamma-S binding; intrinsic efficacy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Rothman, RB NIDA, CPS, IRP, DIR,NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA NIDA POB 5180,5500 Nathan Shock Dr Baltimore MD USA 21224 USA
Citazione:
H. Xu et al., "Opioid peptide receptor studies. 15. Relative efficacy of 4-[(N-allyl-3-methyl-4 piperidinyl) phenylamino]-N,N-diethylbenzamide and related compoundsat the cloned human delta-opioid receptor", SYNAPSE, 40(4), 2001, pp. 269-274

Abstract

Previous data obtained from both binding and functional assays demonstrated that (-)-4-[(N-allyl-3-methyl-4-piperidinyl)phenylamino]-N,N-diethylbenzamide [(-)-RTI5989-54] displays selective binding and full agonist activity relative to (+/-)-RTI5989-54 for the delta opioid receptor. The present study was conducted to evaluate the activities of structurally diverse opioid receptor delta ligands in the [S-35]GTP-gamma -S binding assay, comparing the relationship between receptor binding, activation, efficacy, and intrinsic efficacy. The data, obtained with cloned human delta receptors, demonstrated that (-)-RTI5989-54 behaves like the highly selective delta agonist SNC80. Addition of the hydroxyl group to RTI5989-54 (RTI5989-61) or replacement of the allyl group with the trans-crotyl group on the piperidine nitrogen of RTI-5989-61 (RTI5989-62) increased binding affinity, produced full agonist activity, and decreased intrinsic efficacy at the delta opioid receptor. The order of potency for the EC50 (GTP-gamma -S) was RTI5989-62 (0.20 nM) > RTI5989-61 (0.43 nM) > SNC80 (1.92 nM) > DPDPE (3.50 nM) (-)-RTI5989-54(17.6 nM) > (+/-)-RTI5989-54 (65.6 nM) > (+)-RTI5989-54 (483 nM). RTI5989-61 and RTI5989-62 were fully efficacious, but had intrinsic efficacy valuesthat were 2.2-3.1 times lower than that of DPDPE and SNC80. Comparison of the binding K-i in competitively inhibiting [I-125]IOXY binding to the functional K-i for delta antagonists [Ki (IOXY)/Ki (GTP-gamma -S)] shows that antagonists might antagonize agonist-evoked neurochemical effects with equalmagnitude while occupying different proportions of target receptors. Synapse 40:289-274, 2001, (C) 2001 Wiley-Liss, Inc.dagger

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 16:39:08