Due to necessary maintenance, Xenbase will be unavailable from December 24-29, 2014. We apologize for the inconvenience.

Click on this message to dismiss it.
Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
J Med Chem. September 9, 2010; 53 (17): 6432-44.

p-Trifluoromethyldiazirinyl-etomidate: a potent photoreactive general anesthetic derivative of etomidate that is selective for ligand-gated cationic ion channels.

Husain SS , Stewart D , Desai R , Hamouda AK , Li SG , Kelly E , Dostalova Z , Zhou X , Cotten JF , Raines DE , Olsen RW , Cohen JB , Forman SA , Miller KW .

We synthesized the R- and S-enantiomers of ethyl 1-(1-(4-(3-((trifluoromethyl)-3H-diazirin-3-yl)phenyl)ethyl)-1H-imidazole-5-carboxylate (trifluoromethyldiazirinyl-etomidate), or TFD-etomidate, a novel photoactivable derivative of the stereoselective general anesthetic etomidate (R-(2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate)). Anesthetic potency was similar to etomidate''s, but stereoselectivity was reversed and attenuated. Relative to etomidate, TFD-etomidate was a more potent inhibitor of the excitatory receptors, nAChR (nicotinic acetylcholine receptor) ((alpha1)(2)beta1delta1gamma1) and 5-HT(3A)R (serotonin type 3A receptor), causing significant inhibition at anesthetic concentrations. S- but not R-TFD-etomidate enhanced currents elicited from inhibitory alpha1beta2gamma2L GABA(A)Rs by low concentrations of GABA, but with a lower efficacy than R-etomidate, and site-directed mutagenesis suggests they act at different sites. [(3)H]TFD-etomidate photolabeled the alpha-subunit of the nAChR in a manner allosterically regulated by agonists and noncompetitive inhibitors. TFD-etomidate''s novel pharmacology is unlike that of etomidate derivatives with photoactivable groups in the ester position, which behave like etomidate, suggesting that it will further enhance our understanding of anesthetic mechanisms.

PubMed ID: 20704351
PMC ID: PMC3117435
Article link: J Med Chem.
Grant support: GM 58448 NIGMS NIH HHS , P01 GM058448-13 NIGMS NIH HHS , R01 GM087316 NIGMS NIH HHS , P01 GM058448 NIGMS NIH HHS

Genes referenced:
Antibodies referenced:
Morpholinos referenced:

My Xenbase: [ Log-in / Register ]
version: [3.3]

Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556