Synopsis of calculated lipophilicity, effects on cardiac action potential, and isometric force of rat papillary muscles as well as MDR inhibitory effects of all tested propafenone analogs
KiVmax ± S.E., kaapd50 ± S.E., and kipdf ± S.E. values are given as the result of simultaneous curve fitting of pooled replicate experiments (n = at least 3); IC50 is mean ± S.E.M. of at least two individually fitted daunomycin efflux inhibition experiments.
Compound (Set) | Calculated log P | Effects on Action Potential | Effects on Isometric Force | MDR Inhibition | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| KiVmax | Kaapd50 | KiVmax/Kaapd50 Ratio | Kipdf | Alternans Phenomenon Occurred at Conc. | IC50 Daunomycin Efflux | |||||
| μM | μM | μM | μM | μM | ||||||
| GPV01 | 3.39 | 33.1 ± 2.2 | 275 ± 12 | 0.12 | 173 ± 28 | 100 | 0.70 ± 0.53 | |||
| GPV02 | 3.62 | 28.7 ± 3.8 | 89.2 ± 6.6 | 0.32 | 292 ± 16 | 100 | 0.99 ± 0.26 | |||
| GPV05 | 3.67 | 14.2 ± 3.0 | 39.4 ± 1.7 | 0.36 | 72.9 ± 39 | 30 | 0.66 ± 0.19 | |||
| GPV10 | N.D. | 59.1 ± 10.3 | 207 ± 17 | 0.28 | >1000 | 300 | 3.60 ± 1.47 | |||
| GPV12 | 2.07 | 35.6 ± 9.8 | 306 ± 14 | 0.12 | 577 ± 332 | 1000 | 6.47 ± 1.48 | |||
| GPV29 | 4.43 | >1000 | >1000 | N.D. | >1000 | —a | 0.38 ± 0.104 | |||
| GPV31 | 4.93 | >1000 | >1000 | N.D. | >1000 | — | 0.14 ± 0.06 | |||
| GPV46 | 0.94 | 1118 ± 60 | 2030 ± 141 | 0.55 | 2840 ± 1300 | 1000 | 207 ± 34.7 | |||
| GPV128 | 5.61 | >1000 | >1000 | N.D. | >1000 | — | 0.26 ± 0.05 | |||
| GPV156 | 5.56 | >1000 | >1000 | N.D. | >1000 | — | 0.23 ± 0.11 | |||
| GPV321 | 3.35 | 28.1 ± 1.6 | 30.2 ± 3.4 | 0.93 | 64.4 ± 8.6 | 30 | 0.56 ± 0.29 | |||
| GPV576 | 5.75 | >1000 | >1000 | N.D. | >1000 | — | 0.011 ± 0.001 | |||
| GPV794 | 3.33 | 328 ± 11 | 343 ± 8 | 0.96 | 488 ± 16 | 300 | 0.79 ± 0.08 | |||
N.D., not determined.
↵ a —, no Alternans occurred at highest applicable concentration.