Meert, T.F., and P.A.J. Janssen: The psychopharmacology of ritanserin: comparison with chlordiazepoxide. Drug Dev. Res. 18:119-144, 1989. Ritanserin, a central serotonin 5-HT2 antagonist with complete LSD-antagonist properties, was compared with the benzodiazepine chlordiazepoxide (CDZ) in different animal models of anxiety. In conflict procedures using electric shock as an inhibitory stimulus, a doserelated disinhibition was observed with CDZ but not with ritanserin. In various other anxiety tests involving more natural aversive stimuli, ritanserin disinhibited exploratory behavior over a broad dose range while CDZ was marginally active. Clear differences between ritanserin and CDZ were also seen in drug discrimination test procedures. CDZ but not ritanserin had intrinsic discriminative stimulus properties. Furthermore, ritanserin did not generalize with CDZ or with fentanyl, LSD, cocaine, d-amphetamine, or 8-OHDPAT. These results suggest that ritanserin is unlikely to possess abuse potential. Unlike the benzodiazepine, ritanserin did not induce motor incoordination or sedation, was devoid of interaction with alcohol, and produced no state dependency. These experimental studies indicate that ritanserin possesses disinhibitory effects on exploratory behavior with a profile of activity different from that of benzodiazepines. Ritanserin thus has anxiety-and stress-reducing effects in animal models of anxiety and the drug appears to be an original psychopharmacological compound, clinically characterized as a thymosthenic agent.