Therapeutic Targets Database
BIDD Pharmainformatics Databases


Target Validation Information
Target NameAlpha-2 adrenergic receptor    
Type of TargetSuccessful target    
Drug Potency against TargetClonidineEC50 = 450 nM[1]
DexmedetomidineED50 = 0.001~0.032 mg/kg[2]
ClonidineED50 = 0.0032~1.0 mg/kg[2]
NicergolineIC50 = 22000 nM[3]
YohimbineIC50 = 980 nM[4]
OxymetazolineKi = 0.24 nM[5]
ClonidineKi = 3.8 nM[6]
YohimbineKi = 31 nM[7]
GuanfacinepKi < 6[6]
OxymetazolinepKi < 6[6]
TizanidinepKi = 6.26[6]
GuanabenzpKi = 6.7[6]
DexmedetomidinepKi = 8.64[6]
YohimbinepKi = 8.66[6]
IdazoxanIC50 = 174 nM[8]
Action against Disease ModelGuanfacineEC50 on C fiber compound action potentials of rat sciatic nerves: 170nM[1]
GuanabenzGuanabenz (E-2,6-dichlorobenzylideneaminoguanidine acetate, Wy-8678) and its identified metabolites were tested for their ability to displace clonidine from the cerebral 2-receptors of rat and dog. The Kj's for inhibition of clonidine binding to rat membranes were 1.97, 0.96, 14.0, and 108 nM for clonidine, guanabenz, p-hydroxyguanabenz, and the Z-isomer of guanabenz, respectively. The other metabolites at concentrations of 10,000 nM did not displace clonidine. Scatchard analysis indicated single populations of binding sites with KD' s of 2.37 and 2.39 nM and Bmax's of 5.39 and 5.12 pmol/g for rat and dog preparations, respectively. Hill analysis yielded coefficients approximating unity, indicating a lack of cooperativity in binding. The high affinity of guanabenz relative to that of its metabolites for the 2-receptor provided the basis for the development of an assay capable of discriminating guanabenz from its weakly hypotensive (p-hydroxyguanabenz and the Z-isomer of guanabenz) and pharmacologically inactive (2-6, dichlorobenzyl alcohol,2,6-dichlorobenzaldehyde, 2,6-dichlorobenzaldehyde azine, 2,6-dichlorobenzaldehyde semicarbizone, creatinine adduct of 2,6-dichlorobenzaldehyde, and an isomer of the creatinine adduct) metabolites. Antihypertensive agents with different mechanisms of action such as indoramin, prazosin, debrisoquine, and bethanidine bound little, if at all, and thus will not interfere with the assay of guanabenz.[9]
Oxymetazolineconcentration-related increases in tension of the rat isolated aorta preparation when the drug concentration was increased c uMulatively in the organ bath EC50: 770 nM[10]
Dexmedetomidinesuppressed the amplitude of delayed rectifier K+ current [IK(DR)] in a concentration-dependent manner in NG108-15 cells IC50: 4600 nM[11]
Ref 1Anesth Analg. 1993 Feb;76(2):295-301.The alpha 2-adrenergic agonists clonidine and guanfacine produce tonic and phasic block of conduction in rat sciatic nerve fibers. To Reference
Ref 2Curr Top Med Chem. 2001 Aug;1(3):193-7.Alpha2-adrenergic receptor agonists as analgesics. To Reference
Ref 3Biochemistry. 1977 Nov 1;16(22):4872-9.Hemoglobin Raleigh (beta1 valine replaced by acetylalanine). Structural and functional characterization. To Reference
Ref 4Thromb Res. 2000 Aug 1;99(3):231-7.Atipamezole, an imidazoline-type alpha(2)-adrenoceptor inhibitor, binds to human platelets and inhibits their adrenaline-induced aggregation more effectively than yohimbine. To Reference
Ref 5Curr Top Med Chem. 2002 Jun;2(6):559-74.Recent advances in 5-HT1B/1D receptor antagonists and agonists and their potential therapeutic applications. To Reference
Ref 6Curr Top Med Chem. 2007;7(2):163-86.Agonists and antagonists targeting the different alpha2-adrenoceptor subtypes. To Reference
Ref 7Curr Drug Discov Technol. 2006 Mar;3(1):1-48.Development and validation of an in silico P450 profiler based on pharmacophore models. To Reference
Ref 8J Pharm Pharmacol. 2004 Feb;56(2):213-20.The effects of imidazoline agents on the aggregation of human platelets. To Reference
Ref 9Differential binding of guanabenz and its metabolites to cerebral 2-receptors: The basis for a radioligand assay specific for the drug. Drug Development Research. Volume 3, Issue 1, pages 91C99, 1983 To Reference
Ref 10Selective alpha 1- and alpha 2-adrenoceptor agonist-induced contractions and 45Ca fluxes in the rat isolated aorta. Br J Pharmacol. 1982 December; 77(4): 597C604. To Reference
Ref 11Br J Anaesth. 2009 Aug;103(2):244-54. Epub 2009 Jun 20.Dexmedetomidine, an alpha2-adrenergic agonist, inhibits neuronal delayed-rectifier potassium current and sodium current. To Reference


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