Key result
FG 9202 accumulates ~3-fold in myocardium without causing cardiotoxicity in isolated rabbit hearts.
Why the study?
The cardiac uptake kinetics and potential dynamic effects of the cerebral antiischaemic compound FG 9202 in isolated hearts were not characterized.
Does FG 9202 (NBQX) exhibit cardiotoxicity or alter cardiac dynamics in isolated rabbit hearts?
Does FG 9202 (NBQX) exhibit cardiotoxicity or alter cardiac dynamics in isolated rabbit hearts?
The cerebral antiischaemic compound FG 9202 (NBQX) demonstrates rapid myocardial uptake and clearance without significant cardiotoxicity in an isolated rabbit heart model.
NBQX shows preliminary myocardial safety in vitro; leaves open translation to in vivo or clinical settings.
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 micrograms.ml-1 (119 microM). 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.
No takes yet. Share an insight, caveat, or question.
Nielsen‐Kudsk et al. (1991) studied Isolated rabbit heart (in vitro). FG 9202 (NBQX) was evaluated on Cardiac uptake kinetics and dynamic effects. FG 9202 (NBQX) showed three-compartment kinetics with a steady-state accumulation of about 3 times in the myocardium and was not potentially toxic to the isolated rabbit heart in vitro.