Persson C G, Karlsson J A, Erjefält I
Life Sci. 1982 Jun 21;30(25):2181-9. doi: 10.1016/0024-3205(82)90292-2.
Relaxant effects and adenosine-antagonism of 3-propyl-xanthine (enprofylline) and 10 different methyl-xanthines were examined in isolated guinea-pig tracheas. The chemical structural requirements for tracheal relaxation were found to be different from those for adenosine antagonism by the xanthine derivatives. All xanthines produced relaxation: Enprofylline was about 5 times more potent than theophylline. However, only xanthines with a methyl in the 1-position consistently antagonized the relaxant effect of adenosine. --Theophylline over a wide range of concentrations (30-900 microM) produced a concentration dependent and surmountable antagonism at nervous adenosine receptors (isolated guinea-pig myenteric-plexus preparations). The same concentrations of enprofylline were almost devoid of antagonism at these adenosine receptors. In mice theophylline (6-24 mg/kg given intraperitoneally) dose-dependently increased locomotor activity while enprofylline (2-48 mg/Kg) was without effect on behaviour. "Non-blocking" xanthines such as enprofylline may be potent bronchodilators but lack many theophylline-like actions. We, therefore, forward the hypothesis that universal adenosine antagonism is both unnecessary and undesirable with xanthine antiasthmatics.
在离体豚鼠气管中研究了3-丙基黄嘌呤（恩丙茶碱）和10种不同甲基黄嘌呤的松弛作用及腺苷拮抗作用。发现黄嘌呤衍生物对气管松弛的化学结构要求与腺苷拮抗作用的要求不同。所有黄嘌呤均产生松弛作用：恩丙茶碱的效力约为茶碱的5倍。然而，只有1位带有甲基的黄嘌呤能持续拮抗腺苷的松弛作用。——茶碱在很宽的浓度范围（30 - 900微摩尔）内，对神经腺苷受体（离体豚鼠肠肌丛标本）产生浓度依赖性且可克服的拮抗作用。相同浓度的恩丙茶碱在这些腺苷受体上几乎没有拮抗作用。在小鼠中，茶碱（腹腔注射6 - 24毫克/千克）剂量依赖性地增加运动活性，而恩丙茶碱（2 - 48毫克/千克）对行为无影响。像恩丙茶碱这样的“非阻断性”黄嘌呤可能是强效支气管扩张剂，但缺乏许多茶碱样作用。因此，我们提出这样的假说：对于黄嘌呤类抗哮喘药而言，普遍的腺苷拮抗作用既无必要也不可取。
