Mikus E G, Kapui Z, Korbonits D, Boér K, Boronkay E, Gyürky J, Révész J, Lacheretz F, Pascal M, Arányi P
Laboratory for Respiratory Pharmacology of Research & Development Directorate, Chinoin Pharmaceutical and Chemical Works Co., Ltd., Budapest, Hungary.
Arzneimittelforschung. 1997 Dec;47(12):1358-63.
CH-13584 (formerly: KHL-8425, 1H-purine-2,6-dione, 3,7-dihydro-3-methyl-7[(5-methyl-1,2,4-oxadiazol-3-yl)methyl], CAS 115779-20-9) is a new xanthine derivative, structurally related to theophylline. Potent antitussive activity in the 4 to 8 mg/kg dose range, by the oral route, was already demonstrated for this compound. In the present work, it is shown that contrary to theophylline, CH-13584 does not interact with adenosine A1 receptor and is a weaker inhibitor of cyclic nucleotide phosphodiesterase. In addition, CH-13584 is a less active bronchodilator in vitro and in vivo. It is also devoid of the cardiovascular and behaviour side-effects of theophylline and of effects on diuresis at dosage well above the antitussive dose. CH-13584, therefore, has a different pharmacological profile compared to theophylline and is devoid of the known side-effects of the latter. Such differences could result from a different biochemical profile.
CH - 13584（原名：KHL - 8425，1H - 嘌呤 - 2,6 - 二酮，3,7 - 二氢 - 3 - 甲基 - 7 - [(5 - 甲基 - 1,2,4 - 恶二唑 - 3 - 基)甲基]，CAS 115779 - 20 - 9）是一种新型黄嘌呤衍生物，在结构上与茶碱相关。该化合物经口服途径在4至8毫克/千克剂量范围内已显示出强效镇咳活性。在本研究中，结果表明，与茶碱不同，CH - 13584不与腺苷A1受体相互作用，并且是一种较弱的环核苷酸磷酸二酯酶抑制剂。此外，CH - 13584在体外和体内都是活性较低的支气管扩张剂。在远高于镇咳剂量的给药情况下，它也没有茶碱的心血管和行为副作用以及对利尿的影响。因此，与茶碱相比，CH - 13584具有不同的药理特性，并且没有后者已知的副作用。这些差异可能源于不同的生化特性。
