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Titolo:
STRUCTURE AND PHARMACOLOGY OF 4,5,6,7-TETRAHYDROISOTHIAZOLO[5,4-C]PYRIDIN-3-OL (THIO-THIP), AN AGONIST ANTAGONIST AT GABA(A) RECEPTORS/
Autore:
BREHM L; EBERT B; KRISTIANSEN U; WAFFORD KA; KEMP JA; KROGSGAARDLARSEN P;
Indirizzi:
ROYAL DANISH SCH PHARM,DEPT MED CHEM,UNIV PARKEN 2 DK-2100 COPENHAGENDENMARK ROYAL DANISH SCH PHARM,DEPT MED CHEM DK-2100 COPENHAGEN DENMARK ROYAL DANISH SCH PHARM,DEPT BIOL DK-2100 COPENHAGEN DENMARK MERCK SHARP & DOHME RES LABS,NEUROSCI RES CTR HARLOW CM20 2QR ESSEX ENGLAND
Titolo Testata:
European journal of medicinal chemistry
fascicolo: 4, volume: 32, anno: 1997,
pagine: 357 - 363
SICI:
0223-5234(1997)32:4<357:SAPO4>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
BRAIN GLUCOSE-METABOLISM; EMISSION TOMOGRAPHY PET; EPILEPSY TLE PATIENTS; PARTIAL AGONISTS; ANALOGS; ACTIVATION; RESOLUTION; SUBTYPES; EFFICACY; NEURONS;
Keywords:
GABA(A) RECEPTORS; RECOMBINANT RECEPTORS; RECEPTOR SUBUNITS; MOLECULAR PHARMACOLOGY; CELLULAR ELECTROPHYSIOLOGY; GABA(A) PARTIAL AGONISTS; GABA(A) ANTAGONISTS; STRUCTURE-ACTIVITY STUDIES; HETEROCYCLIC CARBOXYL BIOISOSTERES; X-RAY CRYSTALLOGRAPHY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
63
Recensione:
Indirizzi per estratti:
Citazione:
L. Brehm et al., "STRUCTURE AND PHARMACOLOGY OF 4,5,6,7-TETRAHYDROISOTHIAZOLO[5,4-C]PYRIDIN-3-OL (THIO-THIP), AN AGONIST ANTAGONIST AT GABA(A) RECEPTORS/", European journal of medicinal chemistry, 32(4), 1997, pp. 357-363

Abstract

4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol (Thio-THIP), an analogue of the potent and efficacious partial GABA, agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), shows rather potent agonisteffects at spinal GABA(A) receptors in vivo, but remarkably low affinity for brain GABA(A) receptors in vitro. thyl-4,5,6,7-tetrahydropyrazolo[5,4-c]pyridin-3-ol (2-Me-Aza-THIP) does not bind detectably to GABA(A) receptors. The conformation of the molecule of Thio-THIP, which has now been determined by an X-ray crystallographic analysis, is very similar to those previously described for THIP and 2-Me-Aza-THIP. At human GABA(A) receptors of alpha(3) beta(2) gamma(2) or alpha(5) beta(3) gamma(2) subunit configurations, expressed in Xenopus oocytes, at which THIP shows low- (44%) or high-efficacy (99%) GABA(A) agonism, respectively, Thio-THIP was shown to be a competitive antagonist. At GABA(A) receptors in cultured cerebellar granule cells, Thio-THIP turned out to be a weak low-efficacy (2-9%) partial GABA(A) agonist.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 15:41:40