TABLE 3

Effects of nicardipine and several noscapine derivatives on the rate of ATP hydrolysis by purified, reconstituted P-glycoprotein (P-gp)

The ATPase activity of purified P-gp was measured using a colorimetric assay and plotted as a function of added drug concentration. The general dose-response relationship was fitted to the data to determine the potency to stimulate hydrolysis (EC50) and the extent of stimulation. Values correspond to mean ± S.E.M.

Compound(n)PotencyStimulation
EC50 (μM)Fold basal
Nicardipine(6)2.9 ± 0.5**5.3 ± 0.5
Noscapine(6)44.6 ± 9.13.4 ± 0.4
(2)(3)4.1 ± 1.6**2.5 ± 0.3
(3)(2)65.3 ± 10.24.4 ± 1.3
(4)(3)0.95 ± 0.28**2.4 ± 0.4
(5)(6)18.7 ± 4.5**3.1 ± 0.3
(6)(4)1.0 ± 0.4**1.4 ± 0.9
(7)(6)19.1 ± 1.4**2.7 ± 0.7
(8)(4)10.1 ± 5.3**2.2 ± 0.3
(9)(3)22.5 ± 5.8*2.8 ± 0.6
(10)(4)NENE
(11)(3)NENE
  • (n), Number of independent observations; NE, compound did not alter ATP hydrolysis by G-gp.

  • * Statistically significant difference compared with noscapine (P < 0.05).

  • ** P < 0.01.