Asunto(s)
Azepinas/farmacología , Quinasa de la Caseína II/antagonistas & inhibidores , Naftiridinas/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Receptor Notch1/inmunología , Triazoles/farmacología , Azepinas/agonistas , Quinasa de la Caseína II/genética , Quinasa de la Caseína II/metabolismo , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino , Humanos , Masculino , Naftiridinas/agonistas , Proteínas de Neoplasias/genética , Fenazinas , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Estabilidad Proteica , Receptor Notch1/genética , Triazoles/agonistasRESUMEN
The effect of alpha2-selective adrenoreceptor activation on nasal cavity dimension in an experimental model of congestion has not been defined. Presently, we used acoustic rhinometry to evaluate the decongestant activity of BHT-920, a selective alpha2-adrenergic agonist against nasal congestion produced by intranasal compound 48/80. Administration of the mast cell liberator compound 48/80 (1%) into a nasal passageway decreased ipsilateral volume and minimum cross-sectional area by 73 +/- 4% and 42 +/- 6%, respectively. The congestant effect of compound 48/80 was blocked by topical BHT-920 (0.3 and 1%) in a dose related manner. In addition, the decrease in minimum cross-sectional area produced by compound 48/80 was attenuated after topical BHT-920 treatment. As a comparison we also evaluated the topical decongestant activity effects of the alpha1-adrenergic agonist phenylephrine, and the nonselective alpha-agonist oxymetazoline. Both phenylephrine (0.1-1.0%) and oxymetazoline (0.01-0.3%) produced decongestion. The blood pressure effects of these three drugs also were evaluated. At doses of 0.3 and 1.0%, BHT-920 did not produce hypertension. In contrast, oxymetaZoline (0.01-0.1%) produced a transient hypertension that peaked at 15 minutes and fully recovered 45 minutes after administration. The hypertensive effect of phenylephrine at 0.3 and 1.0% lasted over 60 minutes. The present findings indicate that selective alpha2-agonists may produce decongestant activity with an improved cardiovascular profile compared with current sympathomimetic drugs such as phenylephrine.