TABLE 3.
Effects of specific receptor antagonists on the pharmacokinetics/pharmacodynamics of GHB (1500 mg/kg i.v.)
SCH50911 (150 mg/kg) and bicuculline methiodide (5 mg/kg) were administered intravenously 5 min before GHB. Data are presented as mean (S.D.); n = 3 to 5. One-way analysis of variance followed by Dunnett's post hoc test was used to determine statistically significant differences in mean pharmacokinetic and pharmacodynamic parameters with inhibitor administration compared with those with GHB alone.
| GHB | GHB + SCH50911 | GHB + Bicuculline | |
|---|---|---|---|
| Cl, ml · kg−1 · min−1 | 5.16 (0.70) | 6.07 (0.47) | 5.02 (0.14) |
| ClR, ml · kg−1 · min−1 | 3.18 (0.66) | 2.84 (0.32) | 2.72 (0.78) |
| Clm, ml · kg−1 · min−1 | 1.99 (0.17) | 3.23 (0.78)* | 2.30 (0.63) |
| Frequency ABEC, breaths | 10,500 (2700) | —a | 10,900 (1300) |
| Frequency Emax, breaths/min | 17 (7) | — | 15 (9) |
| Frequency Tmax, min | 53.0 (19) | — | 67.5 (13) |
Significantly different from GHB alone (P < 0.05).
—, no ABEC, Emax, or Tmax values could be calculated because respiration is similar to the baseline values; SCH50911 completely prevented any significant decrease in frequency compared with baseline.