Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report.
J P Zacny, S Yajnik, D Coalson, J L Lichtor, J L Apfelbaum, G Rupani, C Young, P Thapar, J Klafta
Pharmacology, biochemistry, and behavior August 1, 1995 DOI: 10.1016/0091-3057(95)00039-y via PubMed
Summary
AI-generated from the abstractIn two double-blind, randomized, crossover trials, eight healthy volunteers inhaled 30% nitrous oxide in oxygen for 35 minutes and were given flumazenil 10 minutes into the inhalation. Experiment 1 tested clinical doses of flumazenil (0, 0.25, 0.5, and 1.0 mg/70 kg), while Experiment 2 tested a supraclinical dose (0 and 5.0 mg/70 kg). Nitrous oxide increased ratings of high, drunk, and tingling and impaired psychomotor performance. Only the supraclinical flumazenil dose significantly reduced the high rating; other subjective effects showed non-significant decreases. Flumazenil did not affect nitrous oxide's psychomotor effects. The findings suggest that a high flumazenil dose may partially antagonize some subjective effects of nitrous oxide.
Study at a glance
| Characteristics | Double-blind, randomized, crossover trial Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | Healthy volunteers |
| Intervention | Flumazenil |
| Dose | 0, 0.25, 0.5, 1.0, and 5.0 mg/70 kg |
| Duration | 35-minute nitrous oxide inhalation with flumazenil challenge at 10 minutes |
| Key finding | A supraclinical dose of flumazenil (5.0 mg/70 kg) significantly reduced the subjective rating of high produced by nitrous oxide, but did not affect psychomotor impairment. |
Abstract
Two double-blind, randomized, crossover trials were conducted to study whether the benzodiazepine antagonist, flumazenil, would interact with the subjective and psychomotor effects of nitrous oxide in healthy volunteers. In both experiments, eight subjects inhaled 30% nitrous oxide in oxygen for 35 min and were challenged, 10 min into the inhalation, with flumazenil. Experiment 1 tested a range of flumazenil doses used clinically (0, 0.25, 0.5, and 1.0 mg/70 kg) whereas Experiment 2 tested a supraclinical flumazenil dose (0 and 5.0 mg/70 kg). Nitrous oxide increased mood ratings of "high," "drunk," and "tingling," and decreased psychomotor performance as assessed by the Digit Substitution Test. Flumazenil, at the supraclinical dose, significantly lowered the mood rating of "high." Decreases, though not significant (p < 0.10), were also obtained on the ratings "drunk," "elated," and "drug liking". Flumazenil, in both experiments, did not interact with the psychomotor effects of nitrous oxide. It appears that flumazenil, at a dose higher than that used clinically, may antagonize some of the subjective effects produced by nitrous oxide in humans.