THE EFFECTS OF NEW HYPNOTIC DRUGS IN RATS TRAINED TO DISCRIMINATE ETHANOL

Several new, non-benzodiazepine hypnotic drugs have recently been mark eted (zopiclone, zolpidem) or are in development (zaleplon, SX 3228). These compounds act at benzodiazepine (BZ) (omega) receptors but have mechanisms of action which are not identical to those of benzodiazepin es; in particular, zolpidem, zaleplon and SX 3228 have been reported t o have selectivity for the BZ(1) (omega(1)) receptor subtype. In the p resent study the effects of the four hypnotic drugs were investigated in rats trained to discriminate ethanol (1 g/kg). Comparisons were mad e with pentobarbital and the benzodiazepines, lorazepam and midazolam. The two benzodiazepines and the barbiturate produced dose-related sub stitution for ethanol. In contrast, zolpidem, zaleplon, SX 3228 and zo piclone gave rise to only partial (maximum effect 50-67%) substitution , even at doses which greatly reduced rates of lever pressing. The lim ited ethanol-like effects of zolpidem, zaleplon and SX 3228 may be rel ated to the more selective mechanism of action of these compounds. It is not clear why the effects of zopiclone differed from those of the b enzodiazepines.