In vitro and ex vivo inhibition by flutoprazepam of [3H]flunitrazepam binding to mouse brain receptors.

Abstract

The ability of flutoprazepam, a new antianxiety drug of the benzodiazepine class, to inhibit [3H]flunitrazepam binding to mouse brain receptors was investigated in vitro and ex vivo (measurement of [3H]flunitrazepam binding in vitro after in vivo treatment of animals with unlabelled drugs). The Ki values for [3H]flunitrazepam binding in vitro were as follows: flutoprazepam (13.0 nM), diazepam (2.7 nM), nitrazepam (5.3 nM), prazepam (68.5 nM) and chlordiazepoxide (234 nM). Two metabolites of flutoprazepam, N-desalkyl-flutoprazepam (Ki = 3.1 nM) also inhibited [3H]flunitrazepam binding in vitro with higher potencies than that of flutoprazepam. Flutoprazepam was found to be more active in inhibiting [3H]flunitrazepam binding ex vivo and in preventing pentetrazol convulsions than predicted from Ki values. The ID50 values for inhibiting [3H]flunitrazepam binding ex vivo were 0.32 mg/kg, p.o. (flutoprazepam), 0.89 mg/kg, p.o. (diazepam), 0.94 mg/kg, p.o. (nitrazepam), 1.98 mg/kg, p.o. (prazepam) and 23.3 mg/kg, p.o. (chlordiazepoxide), respectively. The correlation between ID50 values ex vivo and ED50 values for preventing pentetrazol convulsions was highly significant (r = 0.929). These results suggest that flutoprazepam can exert its pharmacological activities by itself and that two metabolites also play an important role in the effects of flutoprazepam in vivo.

• Authors: K Oki, T Sukamoto, K Ito, T Nose
• Journal: Archives internationales de pharmacodynamie et de therapie (Arch Int Pharmacodyn Ther) Vol. 269 Issue 2 Pg. 180-6 (Jun 1984) ISSN: 0003-9780 [Print] Belgium
• PMID: 6148044 (Publication Type: Journal Article)

Chemical References

• Anti-Anxiety Agents
• Anticonvulsants
• Benzodiazepinones
• Receptors, Cell Surface
• Receptors, GABA-A
• flutoprazepam
• Flunitrazepam
• Pentylenetetrazole

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Anticonvulsants
• Benzodiazepinones (pharmacology)
• Binding, Competitive
• Brain (metabolism)
• Flunitrazepam (metabolism)
• In Vitro Techniques
• Male
• Membranes (metabolism)
• Mice
• Mice, Inbred Strains
• Pentylenetetrazole (antagonists & inhibitors)
• Receptors, Cell Surface (metabolism)
• Receptors, GABA-A