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Titolo:
CHARACTERIZATION OF CP-122,721 - A NONPEPTIDE ANTAGONIST OF THE NEUROKININ NK1 RECEPTOR
Autore:
MCLEAN S; GANONG A; SEYMOUR PA; BRYCE DK; CRAWFORD RT; MORRONE J; REYNOLDS LS; SCHMIDT AW; ZORN S; WATSON J; FOSSA A; DEPASQUALE M; ROSEN T; NAGAHISA A; TSUCHIYA M; HEYM J;
Indirizzi:
PFIZER INC,DIV CENT RES,DEPT NEUROSCI,EASTERN POINT RD GROTON CT 06340 PFIZER INC,DIV CENT RES,DEPT IMMUNOL GROTON CT 06340 PFIZER INC,DIV CENT RES,DEPT GEN PHARMACOL GROTON CT 06340 PFIZER INC,DIV CENT RES,DEPT MED CHEM GROTON CT 06340 PFIZER INC,DIV CENT RES AICHI 47023 JAPAN
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 277, anno: 1996,
pagine: 900 - 908
SICI:
0022-3565(1996)277:2<900:COC-AN>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
VENTRAL TEGMENTAL AREA; CENTRAL NERVOUS-SYSTEM; SUBSTANCE-P RECEPTORS; TACHYKININ RECEPTORS; NEUROGENIC INFLAMMATION; DOPAMINE RELEASE; BINDING-SITES; RAT; CP-96,345; BRAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
57
Recensione:
Indirizzi per estratti:
Citazione:
S. Mclean et al., "CHARACTERIZATION OF CP-122,721 - A NONPEPTIDE ANTAGONIST OF THE NEUROKININ NK1 RECEPTOR", The Journal of pharmacology and experimental therapeutics, 277(2), 1996, pp. 900-908

Abstract

CP-122,721 [(+)-(2S,3S)-3-(2-methoxy-5-trifluoromethoxybenzyl )amino-2-phenylpiperidine] interacts with high affinity (pIC(50) = 9.8) at the human NK1 receptor expressed in IM-9 cells. In the presence of CP-122,721, there was a reduction in B-max of [I-125]BH-SP binding with no change in affinity suggesting that CP-122,721 does not interact with the NK1 receptor in a competitive manner. In an in vitro functional assay, CP-122,721 blocked SP-induced excitation of locus ceruleus cells in guinea pig brain slices with an IC50 value of 7 nM. In vivo, CP-122,721 potently blocked plasma extravasation in guinea pig lung elicited by aerosolized capsaicin (1 mM) with an ID50 = 0.01 mg/kg, p.o. Orallyadministered CP-122,721 antagonized Sar(9), Met (O-2)(11)-SP-induced locomotor activity in guinea pigs with an ID50 = 0.2 mg/kg suggesting good entry into the central nervous system. In addition, consistent with the insurmountable blockade observed in vitro, CP-122,721 (0.01, 0.03 0.3 mg/kg, p.o.) produced a rightward shift in the dose response curve for SP-induced hypotension in the awake dog that was accompanied by a decrease in the maximal response. Thus, in vitro and in vivo CP-122,721 appears to behave functionally as a noncompetitive antagonist producing an insurmountable blockade of the actions of SP.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 13:42:25