Ro48-6791

Ro48-6791

Identifiers
IUPAC name 3-{5-[(dipropylamino)methyl]-1,2,4-oxadiazol-3-yl}-8-fluoro-5-methyl-4,5-dihydro- 6H-imidazo[1,5-a][1,4]benzodiazepin- 6-one
CAS Number	172407-17-9
PubChem (CID)	9953485
ChemSpider	8129095
Chemical and physical data
Formula	C21H25FN6O2
Molar mass	412.47
3D model (Jmol)	Interactive image
SMILES Fc4cc3c(n2cnc(c1nc(on1)CN(CCC)CCC)c2CN(C3=O)C)cc4
InChI InChI=1S/C21H25FN6O2/c1-4-8-27(9-5-2)12-18-24-20(25-30-18)19-17-11-26(3)21(29)15-10-14(22)6-7-16(15)28(17)13-23-19/h6-7,10,13H,4-5,8-9,11-12H2,1-3H3 Key:NOQIYRGMEFBZTI-UHFFFAOYSA-N
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Ro48-6791 is a drug, an imidazobenzodiazepine derivative developed by Hoffman-LaRoche in the 1990s.^[1]

Ro48-6791 was developed as an alternative to the short-acting imidazobenzodiazepine midazolam, for use in induction of anaesthesia and conscious sedation for minor invasive procedures. Ro48-6791 has properties similar to those of to midazolam, being water-soluble, with a fast onset and short duration of action. It is 4-6x more potent than midazolam,^[2] and slightly shorter acting,^[3] and produces similar side effects such as sedation and amnesia.

It was tested up to Phase II human trials, but while it produced less respiratory depression than propofol, it had a longer recovery time and was deemed not to have any significant advantages over the older drug.^[4] Similarly when Ro48-6791 was compared to midazolam, it had similar efficacy, higher potency and a shorter recovery time, but produced less of a synergistic effect on opioid-induced analgesia and produced more severe side effects such as dizziness after the procedure.^[5] Consequently, it was dropped from clinical development,^[6] although it is still used in scientific research.^[7]

See also

• Benzodiazepine

References

1. US Patent 5665718
2. Dingemanse, J; Van Gerven, JM; Schoemaker, RC; Roncari, G; Oberyé, JJ; Van Oostenbruggen, MF; Massarella, J; Segala, P; et al. (1997). "Integrated pharmacokinetics and pharmacodynamics of Ro 48–6791, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects". British Journal of Clinical Pharmacology. 44 (5): 477–86. doi:10.1046/j.1365-2125.1997.t01-1-00612.x. PMC 2042878. PMID 9384465.
3. Hering, W; Ihmsen, H; Albrecht, S; Schwilden, H; Schüttler, J (1996). "Ro 48-6791 – ein kurzwirksames Benzodiazepin Untersuchungen zur Pharmakokinetik und Pharmakodynamik bei jungen und älteren Probanden im Vergleich mit Midazolam" [RO 48-6791--a short acting benzodiazepine. Pharmacokinetics and pharmacodynamics in young and old subjects in comparison to midazolam]. Der Anaesthesist (in German). 45 (12): 1211–4. doi:10.1007/s001010050360. PMID 9065257.
4. Wrigley, PJ; Elliott, DW; Blake, D (1998). "A phase 2 clinical trial comparing Ro 48-6791, a new short-acting benzodiazepine, with propofol for induction of anaesthesia". Anaesthesia and intensive care. 26 (5): 509–14. PMID 9807605.
5. Tang, J; Wang, B; White, PF; Gold, M; Gold, J (1999). "Comparison of the sedation and recovery profiles of Ro 48-6791, a new benzodiazepine, and midazolam in combination with meperidine for outpatient endoscopic procedures". Anesthesia and Analgesia. 89 (4): 893–8. doi:10.1097/00000539-199910000-00014. PMID 10512261.
6. Gold, ME; Todd, SA; Spiegler, C; Gold, JA (1999). "When the drug trial fails: an approach to clinical drug studies". AANA Journal. 67 (6): 505–12. PMID 10876442.
7. Ihmsen, H; Albrecht, S; Hering, W; Schüttler, J; Schwilden, H (2004). "Modelling acute tolerance to the EEG effect of two benzodiazepines". British Journal of Clinical Pharmacology. 57 (2): 153–61. doi:10.1046/j.1365-2125.2003.01964.x. PMC 1884442. PMID 14748814.