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Titolo:
Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways
Autore:
Haddad, EB; Patel, H; Keeling, JE; Yacoub, MH; Barnes, PJ; Belvisi, MG;
Indirizzi:
UnivLungdon Imperial Coll Sci Technol & Med, Dept Thorac Med, Natl Heart &Univ London Imperial Coll Sci Technol & Med London England SW3 6LY art & Univeartdon Imperial Coll Sci Technol & Med, Dept Cardiothorac Surg, Natl H Univ London Imperial Coll Sci Technol & Med London England SW3 6LY atl H
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 2, volume: 127, anno: 1999,
pagine: 413 - 420
SICI:
0007-1188(199905)127:2<413:PCOTMR>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
IPRATROPIUM BROMIDE; RADIOLIGAND BINDING; TIOTROPIUM BROMIDE; NOCTURNAL ASTHMA; RABBIT LUNG; SUBTYPES; BA-679-BR; DISEASE; METAPROTERENOL; OBSTRUCTION;
Keywords:
human peripheral lung; human airway smooth muscle; glycopyrrolate; ipratropium bromide; muscarinic receptor antagonists; guinea-pig trachea;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Belvisi, MG RhoneEssex,nc Rorer, R&D, Dept Pharmacol, Rainham Rd S, Dagenham RM10 7XS, Rhone Poulenc Rorer Rainham Rd S Dagenham Essex England RM10 7XS
Citazione:
E.B. Haddad et al., "Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways", BR J PHARM, 127(2), 1999, pp. 413-420

Abstract

1 In this study we have evaluated the pharmacological profile of the muscarinic antagonist glycopyrrolate in guinea-pig and human airways in comparison with the commonly used antagonist ipratropium bromide.2 Glycopyrrolate and ipratropium bromide inhibited EFS-induced contractionof guinea-pig trachea and human airways in a concentration-dependent manner. Glycopyrrolate was more potent than ipratropium bromide.3 The onset of action (time to attainment of 50% of maximum response) of glycopyrrolate was similar to that obtained with ipratropium bromide in bothpreparations. In guinea-pig trachea, the offset of action (time taken for response to return to 50% recovery after wash out of the test antagonist) for glycopyrrolate (t(1/2) [offset] = 26.4 +/- 0.5 min) was less than that obtained with ipratropium bromide (81.2 +/- 3.7 min). In human airways, however, the duration of action of glycopyrrolate (t(1/2) [offset] > 96 min) was significantly more prolonged compared to ipratropium bromide (t(1\2) [offset] = 59.2 +/- 17.8 min).4 In competition studies, glycopyrrolate and ipratropium bromide bind human peripheral lung and human airway smooth muscle (HASM) muscarinic receptors with affinities in the nanomolar range (K-i values 0.5-3.6 nM). Similar to ipratropium bromide, glycopyrrolate showed no selectivity in its binding to the M-1-M-3 receptors. Kinetics studies, however, showed that glycopyrrolate dissociates slowly from HASM muscarinic receptors (60% protection against [H-3]-NMS binding at 30 nM) compared to ipratropium bromide.5 These results suggest that glycopyrrolate bind human and guinea-pig airway muscarinic receptors with high affinity. Furthermore, we suggest that the slow dissociation profile of glycopyrrolate might be the underlying mechanism by which this drug accomplishes its long duration of action.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 00:56:04