Modelling of the pharmacodynamic interaction of an A1 adenosine receptor agonist and antagonist in vivo: N6‐cyclopentyladenosine and 8‐cyclopentyltheophylline
Modelling of the pharmacodynamic interaction of an A1 adenosine receptor agonist and antagonist in vivo: N6‐cyclopentyladenosine and 8‐cyclopentyltheophylline
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A1 腺苷受体激动剂和拮抗剂体内药效学相互作用的建模：N6-环戊基腺苷和 8-环戊基茶碱
DOI：
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发表时间：
1995
影响因子：
7.3
通讯作者：
M. Danhof
中科院分区：
文献类型：
--
作者：
S. Appel;R. Mathôt;M. Langemeijer;A. IJzerman;M. Danhof
1 The purpose of this investigation was to develop a pharmacokinetic‐pharmacodynamic model for the interaction between an adenosine A1 receptor agonist and antagonist in vivo. The adenosine A1 receptor agonist, N6‐cyclopentyladenosine (CPA) and the antagonist, 8‐cyclopentyltheophylline (CPT) were used as model drugs. The CPA‐induced reduction in mean arterial pressure and heart rate were used as measurements of effect. 2 Four groups of eight rats each received 200 μg kg−1 of CPA i.v. in 5min during a steady‐state infusion of CPT at a rate of 0, 57, 114 or 228 μg kg−1 h−1. The haemodynamic parameters were continuously measured and frequent blood samples were taken to determine the pharmacokinetics of the drugs. 3 CPT had no influence on the pharmacokinetics of CPA and the baseline values of the haemodynamic variables. Furthermore, no clear antagonism by CPT was observed of the CPA‐induced reduction in mean arterial pressure. However, CPT antagonized the effect on heart rate, and with increasing CPT concentrations, a parallel shift of the CPA concentration‐effect relationship to the right was observed. 4 An agonist‐antagonist interaction model was used to characterize the interaction quantitatively. On the basis of this model, the pharmacodynamic parameters of both CPA and CPT could be estimated. For CPA the values were (mean±s.e.): Emax = 198 ± 11 b.p.m., EC50 = 2.1 ± 0.7ng ml−1, Hill factor = 2.3 ± 0.6 and for CPT: EC50 = 3.7 ± 0.3 ng ml−1 and Hill factor = 3.1 ± 0.1. 5 It is concluded that the competitive agonist‐antagonist interaction model may be of value to characterize quantitatively the pharmacodynamic interactions between adenosine A1 receptor ligands in vivo.
腺苷在肾血流动力学和肾素释放调节中的拟议作用。
DOI：
10.1152/ajprenal.1982.242.5.f423
发表时间：
1982
期刊：
The American journal of physiology
影响因子：
--
作者：
Spielman,WS;Thompson,CI
通讯作者：
Thompson,CI