Table 2.

Zebrafish vs. Tadpole Screening for Hypnotic Activity in GABA_A Receptor Modulators

Zebrafish PMR	Tadpole LoRR
		Yes	No	Total
	Yes	5	0	5
	No	0	6	6
	Total	5	6	11

A set of 11 potent GABA_A receptor modulators (see Table 1 for details and references) were scored as demonstrating or lacking hypnotic activity at 10 μM. Manual tadpole LoRR tests were scored as positive if 5 or more of 10 animals lost righting reflexes after 30 min of immersion in test solution. Zebrafish larvae PMR inhibition was performed on 8 animals per compound with 5 or 6 experimental drugs simultaneously tested against a negative control (E3 buffer with 0.2% DMSO) and a positive control (10 μM etomidate). The PMR outcomes were scored based on ANOVA comparisons to the negative control group (p < 0.05). Concordance between zebrafish larva PMRs and tadpole LoRRs for identifying hypnotics among this group of compounds was 100% (Cohen’s Kappa = 1.000; p = 0.0022 by Fisher’s exact test).