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. Author manuscript; available in PMC: 2010 Oct 28.
Published in final edited form as: Psychopharmacology (Berl). 2009 Mar 10;204(4):667–677. doi: 10.1007/s00213-009-1497-4

Table 3.

Mean ED50 values, dose ratios and respective 95% CL for rate-decreasing effects of flunitrazepam, pregnanolone and ketamine determined before, during and after daily flunitrazepam treatment. During daily treatment with either one or two injections of 1 mg/kg of flunitrazepam, dose-effect curves were determined under two different conditions: when the treatment dose of flunitrazepam was last administered 1 hr before sessions and when the treatment dose flunitrazepam was last administered 25 hr before sessions with flunitrazepam vehicle administered before sessions.

ED50 (mg/kg) Dose ratioa

Value 95% CL Value 95% CL

Flunitrazepam
Before 1.60 0.96-2.23 --
During 1 × 1 mg/kg flunitrazepam
 1 hr 7.59 2.81-12.4 6.88 -1.09-14.84
 25 hr 5.09 1.82-8.37 4.31 -0.05-8.67
During 2 × 1 mg/kg flunitrazepam
 1 hr 11.27* 6.10-16.43 9.53 1.17-17.89
 25 hr 3.84 -0.92-8.59 5.08 -4.17-14.32
After 3.55 1.56-5.53 2.89 0.69-5.08

Pregnanolone
Before 8.52 6.73-10.30 --
During 1 × 1 mg/kg flunitrazepam,
 1 hr 2.10* 1.04-3.16 0.27 0.09-0.45
 25 hr 12.97* 10.65-15.29 1.65 1.12-2.19
During 2 × 1 mg/kg flunitrazepam
 1 hr 7.60 4.16-11.04 0.90 0.53-1.28
 25 hr 13.73* 10.84-16.62 1.70 1.18-2.22
After 9.75 7.83-11.66 1.22 0.82-1.63

Ketamine
Before 1.63 0.99-2.27 --
During 1 × 1 mg/kg flunitrazepam,
 1 hr 2.78* 2.08-3.48 2.12 1.01-3.23
 25 hr 2.13 1.25-3.01 1.65 0.60-2.71
During 2 × 1 mg/kg flunitrazepam
 1 hr 4.99* 2.88-7.10 3.53 1.82-5.24
 25 hr 1.52 0.75-2.30 1.03 0.45-1.61
After 1.32 0.84-1.79 0.89 0.56-1.22
a

Dose ratios are relative to ED50 values determined before treatment.

*

indicates a significant difference from ED50 determined before daily flunitrazepam treatment