Half-lives for mechanism-based inactivation and extent of competitive inhibition of PROD activity, in phenobarbital-induced guinea pig hepatic microsomes, by enantiomers of αMB
| Concentration | (−) αMB | (+) αMB | (±) αMB | |||
|---|---|---|---|---|---|---|
| t1/2 | PROD Activity1-a | t1/2 | PROD Activity1-a | t1/2 | PROD Activity1-a | |
| μM | min | % of control | min | % of control | min | % of control |
| 0.10 | 36.5 ± 8.51-b | 91.7 ± 1.6 | 55.9 ± 10.5 | 83.4 ± 8.4 | 46.2 ± 6.3 | 88.8 ± 8.1 |
| 0.25 | 13.9 ± 1.91-b | 82.7 ± 8.3 | 23.9 ± 6.2 | 71.0 ± 8.0 | 19.3 ± 3.7 | 81.1 ± 7.2 |
| 0.50 | 9.3 ± 2.11-c | 71.7 ± 3.71-b | 14.7 ± 2.2 | 58.8 ± 6.4 | 12.4 ± 1.3 | 62.9 ± 7.1 |
| 1.00 | 6.0 ± 0.5 | 50.5 ± 5.21-b | 7.5 ± 1.0 | 39.1 ± 4.3 | 6.7 ± 0.7 | 48.7 ± 5.2 |
| 2.50 | 1.2 ± 0.11-b | 28.1 ± 3.51-c | 2.6 ± 0.6 | 15.6 ± 4.1 | 1.9 ± 0.7 | 26.4 ± 5.51-b |
↵1-a The extent of competitive inhibition was determined by incubation of microsomes with inhibitor for 5 min at 37°C in the absence of NADPH. The control PROD activities (in the absence of inhibitor) for the experiments with (−) αMB, (+) αMB, and (±) αMB were 247.4 ± 19.7, 262.6 ± 27.9, and 260.0 ± 19.7 pmol/min/nmol of P450, respectively. All values are the mean ± SD of independent experiments performed in duplicate, using liver microsomes prepared from four individual animals (N = 4).
↵1-b Significantly different from (+) αMB, p < 0.05.
↵1-c Significantly different from (+) αMB, p < 0.01.