Contrasting effects of anesthetics in tadpole bioassays

The median anesthetic concentrations (AC 50 values) in the bath solution for loss of righting reflex (RR) or nociceptor response (NR) were determined in larval Rana catesbeiana. The AC50 (NR)/AC50(RR) ratios were between 1.6 and 1.9 for ethanol, ether and diazepam. Comparable ratios for hexobarbital and thiopental were 9.8 and 6.2, which indicated a marked lack of "analgesic" effect. The tadpole AC50 values were consistently higher than AC50 values reported for nonionized and unbound drug in mammalian blood water. The tadpole/mammal ratio for loss of NR during thiopental anesthesia was approximate 8, and analysis of ventricular blood showed that the ultrahigh bath concentrations of thiopental were in equilibrium with those in tadpole serum. The tadpole/mammal ratio for diazepam was approximate 110, and its effect in the tadpole was not reversed by flumazenil. Tadpole/mammal ratios for ethanol and ether were approximate 2. Ethanol and ether showed additive effects when tested in combination, and ethanol-tolerant tadpoles showed a similar tolerance to ether. In contrast, hexobarbital and ethanol showed supra-additive effects, and ethanol-tolerant tadpoles showed a greater tolerance to hexobarbital than to ethanol or ether. These studies show marked differences in effect between barbiturates and the ethanol-ether group, high-concentration benzodiazepine effects presumably independent of a specific receptor, and marked differences in drug potency between amphibia and mammals.