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Titolo:
F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT1B/1D receptors in models relevant to migraine
Autore:
John, GW; Pauwels, PJ; Perez, M; Halazy, S; Le Grand, B; Verscheure, Y; Valentin, JP; Palmier, C; Wurch, T; Chopin, P; Marien, M; Kleven, MS; Koek, W; Assie, MB; Carilla-Durand, E; Tarayre, JP; Colpaert, FC;
Indirizzi:
Ctr Rech Pierre Fabre, F-81106 Castres, France Ctr Rech Pierre Fabre Castres France F-81106 re, F-81106 Castres, France
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 1, volume: 290, anno: 1999,
pagine: 83 - 95
SICI:
0022-3565(199907)290:1<83:F1AN5(>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
C6-GLIAL CELL-LINES; GUINEA-PIG; SEROTONIN RECEPTOR; ANTIMIGRAINE DRUG; SAPHENOUS-VEIN; COMPARATIVE PHARMACOLOGY; ANTAGONIST GR-127,935; TRIGEMINAL GANGLION; CAUSES HYPOTHERMIA; HUMAN 5-HT1D-ALPHA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: John, GW Ctr Rech Pierre Fabre, 17 Ave Jean Moulin, F-81106 Castres, France Ctr Rech Pierre Fabre 17 Ave Jean Moulin Castres France F-81106
Citazione:
G.W. John et al., "F 11356, a novel 5-hydroxytryptamine (5-HT) derivative with potent, selective, and unique high intrinsic activity at 5-HT1B/1D receptors in models relevant to migraine", J PHARM EXP, 290(1), 1999, pp. 83-95

Abstract

F 11356 (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl]benzonitrile) was designed to take advantage of the superior potency and efficacy characteristics of 5-hydroxytryptamine (5-HT) compared with tryptamine at 5-HT1B/1D receptors. F 11356 has subnanomolar affinity for cloned human and nonhuman 5-HT1B and 5-HT1D receptors, and its affinity for 5-HT1A and other 5-HT receptors, including the 5-ht(1F) subtype, is 50-fold lower and micromolar, respectively. In C6 cells expressing human 5-HT1B or human 5-HT1D receptors, F 11356 was the most potent compound in inhibiting forskolin-induced cyclic AMP formation (pD(2) = 8.9 and 9.6), and in contrast to tryptamine and derivatives, it produced maximal enhancement of [S-35]guanosine-5'-O-(3-thio)triphosphate binding equivalent to 5-HT. F 11356 was equipotent to 5-HT (pD(2) = 7.1 versus 7.2) and more potent than tryptamine derivatives in contracting rabbit isolated saphenous vein. In isolated guinea pigtrigeminal ganglion neurons, F 11356 was more potent (pD(2) = 7.3 versus 6.7) and induced greater increases in outward hyperpolarizing Ca2+-dependentK+ current than sumatriptan. In anesthetized pigs, F 11356 elicited highlycranioselective, more potent (from 0.16 mu g/kg i.v.) and greater carotid vasoconstriction than tryptamine derivatives. Decreases in carotid blood flow were observed in conscious dogs from 0.63 mg/kg oral F 11356 in the absence of changes in heart rate or behavior. Oral activity was confirmed when hypothermic responses were elicited in guinea pigs (ED50 = 1.6 mg/kg), suggesting that F 11356 also accesses the brain. F 11356 thus is a selective, high-potency agonist at 5-HT1B/1D receptors, which distinguishes itself fromtryptamine and derivatives in exerting high intrinsic activity at these receptors in Vascular and neuronal models relevant to migraine.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/06/20 alle ore 01:40:18