Ro48-6791

Ro48-6791 is a drug, an imidazobenzodiazepine derivative developed by Hoffman-LaRoche in the 1990s.[1]

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
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H25FN6O2
Molar mass412.47 g·mol−1
3D model (JSmol)
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
  (verify)

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

References
  1. US 5665718
  2. Dingemanse J, van Gerven JM, Schoemaker RC, Roncari G, Oberyé JJ, van Oostenbruggen MF, et al. (November 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 (December 1996). "[RO 48-6791--a short acting benzodiazepine. Pharmacokinetics and pharmacodynamics in young and old subjects in comparison to 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. S2CID 29508.
  4. Wrigley PJ, Elliott DW, Blake D (October 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. doi:10.1177/0310057X9802600506. PMID 9807605.
  5. Tang J, Wang B, White PF, Gold M, Gold J (October 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 (December 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 (February 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.
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