Ro48-6791

Ro48-6791
Identifiers
  • 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 mass412.469 g·mol−1
3D model (JSmol)
  • Fc4cc3c(n2cnc(c1nc(on1)CN(CCC)CCC)c2CN(C3=O)C)cc4
  • 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 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 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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