RESUMO
The usefulness of xanthine bronchodilators in the treatment of asthma is often limited by the side effects of nausea and vomiting. We investigated the mechanism of emesis induced by xanthines, by examining the roles of phosphodiesterase (PDE) inhibition and adenosine antagonism. Theophylline, enprofylline, 8-phenyltheophylline and isobutylmethylxanthine (IBMX), as well as vehicle, were given to ferrets at doses ranging from 0.1 to 150 mg/kg i.p. The potencies of these compounds in producing emetic responses were ranked IBMX greater than enprofylline greater than theophylline greater than 8-phenyltheophylline. These results correlate well with the relative potencies of the compounds as nonselective PDE inhibitors but do not correlate with their relative potencies as adenosine A1 or A2 receptor antagonists. The emetic responses also correlate well with the previously reported potencies of these xanthines as bronchodilators in guinea pigs. We conclude that the emetic side effect of xanthine bronchodilators results from the inhibition of one or more forms of PDE rather than from adenosine antagonism.
