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Titolo:
PHARMACOLOGY OF CP-99,994 - A NONPEPTIDE ANTAGONIST OF THE TACHYKININNEUROKININ-1 RECEPTOR
Autore:
MCLEAN S; GANONG A; SEYMOUR PA; SNIDER RM; DESAI MC; ROSEN T; BRYCE DK; LONGO KP; REYNOLDS LS; ROBINSON G; SCHMIDT AW; SIOK C; HEYM J;
Indirizzi:
PFIZER INC,DEPT NEUROSCI,DIV CENT RES,EASTERN POINT RD GROTON CT 06340 PFIZER INC,DEPT EXPLORATORY MED CHEM,DIV CENT RES GROTON CT 06340 PFIZER INC,DEPT MED CHEM,DIV CENT RES GROTON CT 06340
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 267, anno: 1993,
pagine: 472 - 479
SICI:
0022-3565(1993)267:1<472:POC-AN>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBSTANCE-P RECEPTORS; LOCUS COERULEUS NEURONS; VENTRAL TEGMENTAL AREA; GUINEA-PIG; BINDING-SITES; RAT-BRAIN; MUSCLE MEMBRANES; NK1 RECEPTOR; AUTORADIOGRAPHIC LOCALIZATION; H-3-SUBSTANCE-P BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
62
Recensione:
Indirizzi per estratti:
Citazione:
S. Mclean et al., "PHARMACOLOGY OF CP-99,994 - A NONPEPTIDE ANTAGONIST OF THE TACHYKININNEUROKININ-1 RECEPTOR", The Journal of pharmacology and experimental therapeutics, 267(1), 1993, pp. 472-479

Abstract

2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994) binds selectively and with high affinity (K(i) = 0.25 nM) to neurokinin (NK)-1 tachykinin receptors in a human cell line and in guinea pigs where it acts as an antagonist as evidenced by its blockade of substance P-induced excitation of locus coeruleus neurons in vitro. Subcutaneously administered CP-99,994 antagonized locomotor activity in guinea pigs induced by intraventricular infusion of [Sar-9,Met(O2)11]-substance P (50 mug) with an ID50 = 0.59 mg/kg, indicating that CP-99,994 penetrates into the central nervous system. Orally administered CP-99,994 potently blocked (ID50 = 4 mg/kg) the leakage of Evans blue dye into trachea and bronchi elicited by exposure of guinea pigs to aerosol capsaicin(1 mM). CP-99,994 has reduced affinity (IC50 = 3 muM) for the L-type calcium channel in contrast to CP-96,345 (IC50 = 27 nM) an earlier nonpeptide antagonist. Thus, CP-99,994 represents an important pharmacological tool for investigating the physiological role of substance P anda potentially novel therapeutic agent for treating a variety of diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 16:08:42