Carboetomidate

Carboetomidate
Identifiers
  • ethyl 1-[(1R)-1-phenylethyl]pyrrole-2-carboxylate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC15H17NO2
Molar mass243.306 g·mol−1
3D model (JSmol)
  • CCOC(=O)C1=CC=CN1[C@H](C)C2=CC=CC=C2
  • InChI=1S/C15H17NO2/c1-3-18-15(17)14-10-7-11-16(14)12(2)13-8-5-4-6-9-13/h4-12H,3H2,1-2H3/t12-/m1/s1
  • Key:YRYOWTHHYBWOJL-GFCCVEGCSA-N

Carboetomidate is an anesthetic drug derived from etomidate. It is an analogue of etomidate where one of the nitrogen atoms in the imidazole ring has been replaced by carbon to make it a pyrrole ring. This almost completely eliminates the enzyme inhibitory activity which is responsible for most of the problematic side effects of etomidate, in particular its suppression of corticosteroid synthesis which also leads to inhibited production of other steroid hormones. However, while this makes carboetomidate significantly more selective than etomidate as a positive allosteric modulator of β2/β3 containing GABAA receptors, it also confers activity as an antagonist of 5-HT3 serotonin receptors and α4β2 nicotinic acetylcholine receptors which etomidate does not possess. This could have some advantages, but would also cause carboetomidate to have a different side effect profile of its own, and so it has not been developed for clinical use in humans, though it continues to be used in research into this family of compounds.

See also

References

  1. ↑ Sneyd JR, Rigby-Jones AE (September 2010). "New drugs and technologies, intravenous anaesthesia is on the move (again)". British Journal of Anaesthesia. 105 (3): 246–254. doi:10.1093/bja/aeq190. PMID 20650920.
  2. ↑ Cotten JF, Forman SA, Laha JK, Cuny GD, Husain SS, Miller KW, et al. (March 2010). "Carboetomidate: a pyrrole analog of etomidate designed not to suppress adrenocortical function". Anesthesiology. 112 (3): 637–644. doi:10.1097/ALN.0b013e3181cf40ed. PMC 2830733. PMID 20179500.
  3. ↑ Sneyd JR (2012). "Novel etomidate derivatives". Current Pharmaceutical Design. 18 (38): 6253–6256. doi:10.2174/138161212803832362. PMID 22762475.
  4. ↑ Pejo E, Feng Y, Chao W, Cotten JF, Le GE, Raines DE (January 2012). "Differential effects of etomidate and its pyrrole analogue carboetomidate on the adrenocortical and cytokine responses to endotoxemia". Critical Care Medicine. 40 (1): 187–192. doi:10.1097/CCM.0b013e31822d7924. PMC 3242859. PMID 21926608.
  5. ↑ Pierce DW, Pejo E, Raines DE, Forman SA (July 2012). "Carboetomidate inhibits alpha4/beta2 neuronal nicotinic acetylcholine receptors at concentrations affecting animals". Anesthesia and Analgesia. 115 (1): 70–72. doi:10.1213/ANE.0b013e318254273e. PMC 3381859. PMID 22543065.
  6. ↑ Desai R, Miller KW, Raines DE (March 2013). "The pyrrole etomidate analog carboetomidate potently inhibits human 5-HT3A receptor function: comparisons with etomidate and potential implications for emetogenesis". Anesthesia and Analgesia. 116 (3): 573–579. doi:10.1213/ANE.0b013e31827d204d. PMC 3582768. PMID 23400978.