Comparison of the in vitro pharmacological profiles of long-acting muscarinic antagonists in human bronchus.
Pulm Pharmacol Ther
; 49: 46-53, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29337266
ABSTRACT
BACKGROUND AND PURPOSE:
Long-acting muscarinic antagonists (LAMAs) have been recommended for the treatment of chronic obstructive pulmonary disease and (more recently) asthma. However, the in vitro pharmacological profiles of the four LAMAs currently marketed (tiotropium, umeclidinium, aclidinium and glycopyrronium) have not yet been compared (relative to ipratropium) by using the same experimental approach. EXPERIMENTALAPPROACH:
With a total of 560 human bronchial rings, we investigated the antagonists' potency, onset and duration of action for inhibition of the contractile response evoked by electrical field stimulation. We also evaluated the antagonists' potency for inhibiting cumulative concentration-contraction curves for acetylcholine and carbachol. KEYRESULTS:
The onset and duration of action were concentration-dependent. At submaximal, equipotent concentrations, the antagonists' onsets of action were within the same order of magnitude. However, the durations of action differed markedly. After washout, ipratropium's inhibitory activity decreased rapidly (within 30-90â¯min) but those of tiotropium and umeclidinium remained stable (at above 70%) for at least 9â¯h. Aclidinium and glycopyrronium displayed less stable inhibitory effects, with a progressive loss of inhibition at submaximal concentrations. In contrast to ipratropium, all the LAMAs behaved as insurmountable antagonists by decreasing the maximum responses to both acetylcholine and carbachol. CONCLUSIONS AND IMPLICATIONS The observed differences in the LAMAs' in vitro pharmacological profiles in the human bronchus provide a compelling pharmacological rationale for the differences in the drugs' respective recommended daily doses and frequencies of administration.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Bronquios
/
Ipratropio
/
Antagonistas Muscarínicos
Límite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pulm Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article