Effect of Newly Synthesized Compounds 44Bu and 444 on QRS-Complex Width and Fast Sodium Current: Differences between Isomers
| Authors | |
|---|---|
| Year of publication | 2010 |
| Type | Article in Periodical |
| Magazine / Source | Acta Veterinaria Brno |
| MU Faculty or unit | |
| Citation | |
| Doi | http://dx.doi.org/10.2754/avb201079010041 |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | 444; 44Bu; isomer; QRS-complex; sodium current; rat |
| Description | In this study, we explored the effect of both racemates and particular isomers of 44Bu and 444 on the QRS-complex width in vivo in rats and on INa in isolated rat ventricular myocytes. All variants of 44Bu and 444 (1.5 mg/kg) caused a significant QRS-widening reaching the peak effect at the 1st or 2nd min after their intravenous administration. 44Bu racemate widened the QRS-complex by 57%, significantly more than R- (33%-widening) and S-isomer (36%-widening). 444 racemate widened the QRS-complex by 64%, which was comparable to S-isomer (63%-widening), however, substantially more than R-isomer (40%-widening). Regarding the effect on INa, 44Bu caused a significantly deeper INa-block compared to 444 in the same concentration of 3.0 micromol/l (0.1 mg/kg). 44Bu racemate and R-isomer blocked INa similarly (91.7 and 91.8%-block, respectively), significantly more than S-isomer (82.4%-block). 444 R-isomer blocked INa less than racemate and S-isomer (by 31.7% vs. 48.3 and 50.2%, respectively). |
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