Psychopharmacology of ritanserin: Comparison with chlordiazepoxide

Abstract

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.

Ritanserin, a new therapeutic approach for drug abuse. Part 3: Effects on fentanyl and sucrose

“…In conclusion, the antidepressant ritanserin [Meert and Janssen, 1989;Reyntjens et al, 19861 is demonstrated here to reduce fentanyl intake and fentanyl preference in rats without interfering with consumatory physiological processes and without having any direct interaction with fentanyl. Because similar results were reported for ritanserin against cocaine and alcohol but not against sucrose, it appears that ritanserin may change or influence basic mechanisms responsible for the need for drug reinforcement after a chronic exposure to that particular drug of abuse.…”

Functional study of rat 5‐HT2A receptors using antisense oligonucleotides

“…The apparatus used for the elevated plus‐maze test has been described by Meert and Janssen (1989). The elevated plus‐maze was made of Perspex, with two opposite open arms (50 × 10 cm) and two opposite closed arms of the same size with walls of 50 cm high.…”

Neuropharmacological aspects of adaptive pain inhibition in murine “victims” of aggression

“…It is beyond the scope of the present article to review in detail the new evidence linking 5-HT to anxiety and the mechanisms of action of antianxiety drugs. However, a substantial body of evidence supports a prominent role for 5-HT, and (to a lesser extent) 5-HT3 receptors in anxiety: in contrast, the supporting case for 5-HT2 receptor involvement in anxiety is weak at best [for reviews see Handley and McBlane, 1993;Meert and Janssen, 1989;Rodgers and Cooper, 19911. In view of these developments, and to further our understanding of the mechanisms involved, we have conducted a detailed series of studies on the effects of 5-HT receptor ligands on non-opioid defensive analgesia in intruder mice.…”