CARDIAC UPTAKE KINETICS AND POSSIBLE DYNAMIC EFFECTS OF A NEW CEREBRAL ANTIISCHEMIC COMPOUND FG-9202 (NBQX) STUDIED IN THE ISOLATED RABBIT HEART

被引:2
作者
NIELSENKUDSK, F
MELLEMKJAER, S
BANG, L
机构
[1] Institute of Pharmacology, University of Aarhus, Aarhus
来源
PHARMACOLOGY & TOXICOLOGY | 1991年 / 69卷 / 02期
关键词
D O I
10.1111/j.1600-0773.1991.tb01285.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Accumulation of the putative drug FG 9202 in isolated rabbit hearts showed monophasic exponential kinetics with a half-life of only 0.59 min. The disposition showed a three-phasic exponential time course with half-lives of 0.34, 1.51 and 15.8 min, respectively, which was interpreted as three-compartment kinetics. FG 9202 accumulated only about 3 times in the myocardium at steady-state with 51, 32 and 17% referable to a superficial and two deeper myocardial drug pools. The drug did not significantly affect contraction amplitude or velocity of contraction at increasing concentrations up to 40.6-mu-g.ml-1 (119-mu-M). Heart beating frequency decreased slightly but only significantly at some of the higher concentrations. Neither dromotropic, bathmotropic nor ischaemic ECG-effects were observed. Coronary flow-rate and myocardial oxygen consumption decreased at the highest drug concentrations. Myocardial efficiency expressed as the ratio of contractile parameters to oxygen consumption showed a minor but insignificant increase at the highest drug-exposure levels. Our findings indicate that FG 9202 is not potentially toxic to the isolated, spontaneously beating rabbit heart in vitro.
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收藏
页码:127 / 131
页数:5
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