Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Affinity for the P-glycoprotein efflux pump at the blood-brain barrier mayexplain the lack of CNS side-effects of modern antihistamines
Autore:
Chishty, M; Reichel, A; Siva, J; Abbott, NJ; Begley, DJ;
Indirizzi:
Univ London Kings Coll, GKT Sch Biomed Sci, Ctr Res Neurosci, Blood Brain Barrier Res Grp, London SE1 1UL, England Univ London Kings Coll London England SE1 1UL p, London SE1 1UL, England
Titolo Testata:
JOURNAL OF DRUG TARGETING
fascicolo: 3, volume: 9, anno: 2001,
pagine: 223 - 228
SICI:
1061-186X(2001)9:3<223:AFTPEP>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL-CELLS; HISTAMINE; DRUGS; H-1-ANTAGONISTS; DEXAMETHASONE; TERFENADINE; SENSITIVITY; LINE;
Keywords:
antihistamine; blood-brain barrier; CNS side-effects; P-glycoprotein; sedation; RBE4;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Chishty, M Univ London Kings Coll, GKT Sch Biomed Sci, Ctr Res Neurosci, Blood Brain Barrier Res Grp, Hodgkin Bldg,Guys Campus, London SE1 1UL, England Univ London Kings Coll Hodgkin Bldg,Guys Campus London England SE1 1UL
Citazione:
M. Chishty et al., "Affinity for the P-glycoprotein efflux pump at the blood-brain barrier mayexplain the lack of CNS side-effects of modern antihistamines", J DRUG TAR, 9(3), 2001, pp. 223-228

Abstract

First generation Hl receptor antagonists are often associated with adverseCNS effects such as sedation, whereas modem, second generation antihistamines are generally non-sedating. The difference in therapeutic profile is mainly due to the poor CNS penetration of the modem derivatives. Current explanations for the differential ability of classical and modem antihistaminesto cross the blood-brain barrier (BBB), based on differences in lipophilicity or protein binding, are inadequate. We have tested the hypothesis that non-sedating antihistamines fail to enter the CNS due to recognition by theP-glycoprotein (Pgp) drug efflux pump expressed on the luminal surface of cerebral endothelial cells forming the BBB in vivo. The ability of several sedating and non-sedating antihistamines to affect the uptake of the Pgp model substrate [H-3]-colchicine was examined using the immortalised rat brain endothelial cell line, RBE4, an established in vitro model of the BBB expressing Pq. All second generation antihistamines tested, significantly increased net accumulation of [H-3]-colchicine to a level similar to that caused by the Pgp inhibitor verapamil. By contrast, the first generation antihistamines showed no affinity for Pgp. The results indicate that differences in the ability of classical and modem antihistaminesto interact with Pgp at the BBB may determine their CNS penetration and asa consequence the presence or absence of central side-effects.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/08/20 alle ore 21:37:11