Action and disposition of the ß3-agonist nebivolol in the presence of inflammation; an alternative to conventional ß1-blockers.
Curr Pharm Des
; 20(9): 1311-7, 2014.
Article
en En
| MEDLINE
| ID: mdl-23978104
Inflammation reduces pharmacological response to ß1-blockers by down-regulating the target receptor protein. This may contribute to the sub-optimal response to pharmacotherapy with ß-blockers. Nebivolol is a third generation ß-adrenoceptor (AR) blocker with high selectivity for blocking ß1 and ß3-agonistic properties. We studied whether response to nebivolol is also reduced by inflammation. Male Sprague-Dawley rats (Inflamed; Mycobacterium butyricum induced) and Control (healthy) were orally administered single doses of 2 mg/kg nebivolol (n=5) or 25 mg/kg propranolol (positive control, n=7-8); ECG recorded for PR and RR interval measurements; serial blood samples were collected for pharmacokinetic assessment. Subsequently, the myocardial ß1, ß2 and ß3-AR levels were measured in homogenized hearts. For propranolol, inflammation resulted in increased concentration but reduced response and down-regulation of ß1- AR. The action and disposition of nebivolol were, however, unaffected by inflammation despite the reduced ß1-AR levels. The levels of ß2 and ß3-AR were unaffected by inflammation. The consistency of response to nebivolol despite inflammation may be due to the predominance of contribution of ß2 and ß3-AR. The lack of an inhibitory effect of inflammation on the clearance of nebivolol is suggestive of mechanisms other than an efficient hepatic metabolism for its low bioavailability. If extrapolated to human, nebivolol may be a more effective cardiovascular drug when inflammatory conditions are present.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Propranolol
/
Benzopiranos
/
Etanolaminas
/
Agonistas de Receptores Adrenérgicos beta 3
/
Inflamación
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Curr Pharm Des
Asunto de la revista:
FARMACIA
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Emiratos Árabes Unidos