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Titolo:
STUDIES ON THE PHARMACOLOGY OF THE NOVEL HISTAMINE H-3 RECEPTOR AGONIST SCH-50971
Autore:
HEY JA; ASLANIAN R; BOLSER DC; CHAPMAN RW; EGAN RW; RIZZO CA; SHIH NY; FERNANDEZ X; MCLEOD RL; WEST R; KREUTNER W;
Indirizzi:
SCHERING PLOUGH CORP,RES INST,ALLERGY,2015 GALLOPING HILL RD KENILWORTH NJ 07033
Titolo Testata:
Arzneimittel-Forschung
fascicolo: 9, volume: 48, anno: 1998,
pagine: 881 - 888
SICI:
0004-4172(1998)48:9<881:SOTPOT>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN CORTEX; GUINEA-PIG; SEROTONIN RELEASE; MAMMALIAN BRAIN; INHIBITION; SUBTYPES; BINDING; ANTAGONIST; STRIATUM; INVITRO;
Keywords:
CAS 75614-87-8; CAS 167610-28-8; HISTAMINE H-3 RECEPTORS, AGONISTS; (R)-ALPHA-METHYLHISTAMINE; RANS-4-(4(R)-METHYL-3(R)-PYROLIDINYL)-1H-IMIDAZOLE DIHYDROCHLORIDE; SCH 50971, PHARMACOLOGY, PREJUNCTIONAL INHIBITION; SYMPATHOINHIBITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
J.A. Hey et al., "STUDIES ON THE PHARMACOLOGY OF THE NOVEL HISTAMINE H-3 RECEPTOR AGONIST SCH-50971", Arzneimittel-Forschung, 48(9), 1998, pp. 881-888

Abstract

Experiments were performed to characterize the pharmacology of Sch 50971 trans-4(4(R)-methyl-3(R)-pyrolidinyl)-1H-imidazole dihydrochloride, CAS 167610-28-8), a novel histamine H-3 receptor agonist. The activity of Sch 50971 was compared with that of (R)-alpha-methylhistamine (CAS 75614-87-8), a potent and moderately selective agonist of histamineH-3 receptors, in a series of in vitro and in vivo assays. Sch 50971 is a high affinity, selective H-3 receptor agonist in vitro and in vivo. Sch 50971 inhibits [H-3]-N-alpha-methylhistamine (CAS 67350-7) binding to the histamine H-3 receptor in human brain (Ki = 5.0 nmol/l) andguinea pig brain (Ki = 2.5 nmol/l). Sch 50971 also inhibits electric field stimulated guinea pig ileum contractions (pD(2) = 7.47) and decreases [H-3]-norepinephrine (CAS 51-41-2) release (pD(2) = 7.48) from guinea pig pulmonary artery by activation of presynaptic inhibitory H-3receptors. The in vitro effects of Sch 50971 are antagonized by low concentrations of a selective H-3 antagonist, thioperamide (CAS 106243-16-7). Sch 50971 has low affinity (IC50's > 10 mu mol/l) for histamineH-1, dopamine D-1 and D-2, serotonin 5-HT2 and muscarinic cholinergicreceptors. It also does not exhibit histamine H-2-antagonist activity. In guinea pigs and cats, Sch 50971 exhibits in vivo H-3 agonist activity. Sch 50971 inhibits sympathetic hypertension evoked by stimulation of the medulla oblongata in anesthetized guinea pigs (ED30 = 0.3 mg/kg i.v., ED30 = 1.0 mg/kg i.d.). Sch 50971 also inhibits the effects of sympathetic nerve stimulation on nasal resistance in cats. In these assays, Sch 50971 exhibits an efficacy and potency comparable to H-3-agonist (R)-alpha-methylhistamine. However, under in vivo conditions, Sch 50971 does not exhibit histamine H-3-mediated responses that are seen with (R)-alpha-methylhistamine at Closes close to those that produce H-3 effects. Therefore, Sch 50971 is a novel, potent and selective agonist of histamine H3 receptors with an improved in vitro and in vivoreceptor profile selectivity compared with (R)-alpha-methylhistamine.

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Documento generato il 24/01/21 alle ore 04:43:25