Howell R E, Muehsam W T, Kinnier W J
NOVA Pharmaceutical Corporation, Baltimore, Maryland 21224.
Life Sci. 1990;46(8):563-8. doi: 10.1016/0024-3205(90)90123-9.
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.
黄嘌呤类支气管扩张剂在治疗哮喘时的效用常常受到恶心和呕吐等副作用的限制。我们通过研究磷酸二酯酶（PDE）抑制作用和腺苷拮抗作用的角色，来探究黄嘌呤类药物引发呕吐的机制。将氨茶碱、恩丙茶碱、8-苯基茶碱和异丁基甲基黄嘌呤（IBMX）以及赋形剂以0.1至150mg/kg的腹腔注射剂量给予雪貂。这些化合物引发呕吐反应的效力排序为：IBMX＞恩丙茶碱＞氨茶碱＞8-苯基茶碱。这些结果与这些化合物作为非选择性PDE抑制剂的相对效力密切相关，但与它们作为腺苷A1或A2受体拮抗剂的相对效力无关。呕吐反应也与先前报道的这些黄嘌呤类药物在豚鼠体内作为支气管扩张剂的效力密切相关。我们得出结论，黄嘌呤类支气管扩张剂的呕吐副作用是由一种或多种形式的PDE抑制引起的，而非腺苷拮抗作用。
