In vivo saturation binding of GABA-A receptor ligands to estimate receptor occupancy using liquid chromatography/tandem mass spectrometry

Biopharmaceutics and Drug Disposition

Volumn 30, Issue 1, 2009, Pages 9-20

  Hopkins, Seth C ^a,c   Nofsinger, J Brian ^b   Allen, Michael S ^b   Koch, Patrick ^a   Varney, Mark A ^a,d  

^a DAINIPPON SUMITOMO PHARMA CO LTD   (Japan)

^b Enthalpy Analytical Inc   (United States)

^c Cortex Pharmaceuticals ^*  (United States)

^d NONE   (United States)

Author keywords

Benzodiazepines; GABA A; LC MS MS; Occupancy; Saturation binding

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; 7 TERT BUTYL 3 (2,5 DIFLUOROPHENYL) 6 (2 METHYL 2H 1,2,4 TRIAZOL 3 YLMETHOXY) 1,2,4 TRIAZOLO[4,3 B]PYRIDAZINE; FLUMAZENIL; GABAERGIC RECEPTOR AFFECTING AGENT; TRITIUM; ZOLPIDEM; ZOPICLONE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DOSE RESPONSE; DRUG ANTAGONISM; DRUG BINDING SITE; DRUG BLOOD LEVEL; DRUG DETERMINATION; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG INFORMATION; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; IN VIVO STUDY; INTERMETHOD COMPARISON; LIGAND BINDING; LIQUID CHROMATOGRAPHY; MALE; MEMBRANE BINDING; MOUSE; NONHUMAN; RACEMIC MIXTURE; SINGLE DRUG DOSE; STEREOCHEMISTRY; TANDEM MASS SPECTROMETRY;

ALGORITHMS; ANIMALS; AZABICYCLO COMPOUNDS; BINDING SITES; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; FLUMAZENIL; FLUOROBENZENES; GABA AGONISTS; GABA MODULATORS; HYPNOTICS AND SEDATIVES; INDICATORS AND REAGENTS; LIGANDS; MALE; MICE; MODELS, STATISTICAL; PIPERAZINES; PYRIDINES; RECEPTORS, GABA-A; STEREOISOMERISM; TANDEM MASS SPECTROMETRY; TRIAZOLES;

EID: 59949088238     PISSN: 01422782     EISSN: 1099081X     Source Type: Journal    
DOI: 10.1002/bdd.641     Document Type: Article

References (37)

1. Sigel E. Mapping of the benzodiazepine recognition site on GABA(A) receptors. Curr Top Med Chem 2002; 2: 833-839.
2. Cromer BA, Morton CJ, Parker MW. Anxiety over GABA(A) receptor structure relieved by AChBP. Trends Biochem Sci 2002; 27: 280-287.
3. Chou KC. Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5. Biochem Biophys Res Commun 2004; 316: 636-642.
4. Hevers W, Luddens H. The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes. Mol Neurobiol 1998; 18: 35-86.
5. Martin JR, Schoch P, Jenck F, Moreau JL, Haefely WE. Pharmacological characterization of benzodiazepine receptor ligands with intrinsic efficacies ranging from high to zero. Psychopharmacology (Berl) 1993; 111: 415-422.
6. Facklam M, Schoch P, Bonetti EP et al. Relationship between benzodiazepine receptor occupancy and functional effects in vivo of four ligands of differing intrinsic efficacies. J Pharmacol Exp Ther 1992; 261: 1113-1121.
7. Dubinsky B, Vaidya AH, Rosenthal DI et al. 5-Ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydro- benzo[4,5]imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)-carboxamide (RWJ-51204), a new nonbenzodiazepine anxiolytic. J Pharmacol Exp Ther 2002; 303: 777-790.
8. van Steveninck AL, Gieschke R, Schoemaker RC et al. Pharmacokinetic and pharmacodynamic interactions of bretazenil and diazepam with alcohol. Br J Clin Pharmacol 1996; 41: 565-573.
9. Stanley JL, Lincoln RJ, Brown TA, McDonald LM, Dawson GR, Reynolds DS. The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines. J Psychopharmacol 2005; 19: 221-227.
10. Abadie P, Rioux P, Scatton B et al. Central benzodiazepine receptor occupancy by zolpidem in the human brain as assessed by positron emission tomography. Eur J Pharmacol 1996; 295: 35-44.
11. Benavides J, Peny B, Dubois A et al. In vivo interaction of zolpidem with central benzodiazepine (BZD) binding sites (as labeled by [3H]Ro 15-1788) in the mouse brain. Preferential affinity of zolpidem for the omega 1 (BZD1) subtype. J Pharmacol Exp Ther 1988; 245: 1033-1041.
12. Scott-Stevens P, Atack JR, Sohal B, Worboys P. Rodent pharmacokinetics and receptor occupancy of the GABAA receptor subtype selective benzodiazepine site ligand L-838417. Biopharm Drug Dispos 2005; 26: 13-20.
13. Brown CL, Martin IL. Kinetics of [3H]Ro 15-1788 binding to membrane-bound rat brain benzodiazepine receptors. J Neurochem 1984; 42: 918-923.
14. Goeders NE, Kuhar MJ. Benzodiazepine receptor binding in vivo with [3H]-Ro 15-1788. Life Sci 1985; 37: 345-355.
15. Miller LG, Greenblatt DJ, Paul SM, Shader RI. Benzodiazepine receptor occupancy in vivo: correlation with brain concentrations and pharmacodynamic actions. J Pharmacol Exp Ther 1987; 240: 516-522.
16. Potier MC, Prado de Carvalho L, Dodd RH, Brown CL, Rossier J. In vivo binding of [3H]Ro 15-1788 in mice: comparison with the in vivo binding of [3H]flunitrazepam. Life Sci 1988; 43: 1287-1296.
17. Atack JR, Smith AJ, Emms F, McKernan RM. Regional differences in the inhibition of mouse in vivo [3H]Ro 15-1788 binding reflect selectivity for alpha 1 versus alpha 2 and alpha 3 subunit-containing GABAA receptors. Neuropsychopharmacology 1999; 20: 255-262.
18. Li J, Fish RL, Cook SM, Tattersall FD, Atack JR. Comparison of in vivo and ex vivo [3H]flumazenil binding assays to determine occupancy at the benzodiazepine binding site of rat brain GABAA receptors. Neuropharmacology 2006; 51: 168-172.
19. Chernet E, Martin LJ, Li D et al. Use of LC/MS to assess brain tracer distribution in preclinical, in vivo receptor occupancy studies: dopamine D2, serotonin 2A and NK-1 receptors as examples. Life Sci 2005; 78: 340-346.
20. Blaschke G, Hempel G, Müller WE. Preparative and analytical separation of the zopiclone enantiomers and determination of their affinity to the benzodiazepine receptor binding site. Chirality 1993; 5: 419-421.
21. Fahey JM, Grassi JM, Reddi JM, Greenblatt DJ. Acute zolpidem administration produces pharmacodynamic and receptor occupancy changes at similar doses. Pharmacol Biochem Behav 2006; 83: 21-27.
22. Pike A, Cook SM, Watt AP et al. Contribution of specific binding to the central benzodiazepine site to the brain concentrations of two novel benzodiazepine site ligands. Biopharm Drug Dispos 2007; 28: 275-282.
23. Millet P, Graf C, Buck A et al. Similarity and robustness of PET and SPECT binding parameters for benzodiazepine receptors. J Cereb Blood Flow Metab 2000 20: 1587-1603.
24. Giroud C, Augsburger M, Menetrey A, Mangin P. Determination of zeleplon and zolpidem by liquid chromatography-turbo-ionspray mass spectrometry: application to forensic cases. J Chromatogr B 2003; 789: 131-138.
25. Kratzsch C, Tenberken O, Peters FT, Weber AA, Kraemer T, Maurer H. Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization. J Mass Spectrom 2004; 39: 856-872.
26. Kintz P, Villain M, Conchiero M, Cirimele V. Screening and confirmatory method for benzodiazepines and hypnotics in oral fluid by LC/MS/MS. Forensic Sci Int 2005; 150: 213-220.
27. Smyth WF, Joyce C, Ramachandran VN, O'Kane E, Coulter D. Characterisation of selected hypnotic drugs and their metabolites using electrospray ionization with ion trap mass spectrometry and with quadrupole time-of-flight mass spectrometry and their determination by liquid chromatography-electrospray ionisation-ion trap mass spectrometry. Anal Chim Acta 2004; 506: 203-214.
28. Kintz P, Villain M, Ludes B. Testing for zolpidem in oral fluid by liquid chromatography-tandem mass spectrometry. J Chromatogr B 2004; 811: 59-63.
29. Villain M, Cheze M, Tracqui A, Ludes B, Kintz P. Windows of detection of zolpidem in urine and hair: application to two drug facilitated sexual assaults. Forensic Sci Int 2004; 143: 157-161.
30. Villain M, Cheze M, Tracqui A, Ludes B, Kintz P. Testing for zopiclone in hair application to drug-facilitated crimes. Forensic Sci Int 2004; 145: 117-121.
31. Villain M, Concheiro M, Cirimele V, Kintz P. Screening method for benzodiazepines and hypnotics in hair at pg/mg level by liquid chromatography-mass spectrometry/mass spectrometry. J Chromatogr B 2005; 825: 72-78.
32. Fernandez C, Baune B, Gimenez F, Thuillier A, Farinotti R. Determination of zopiclone enantiomers in plasma by liquid chromatography using a chiral cellulose carbamate column. J Chromatogr 1991; 572: 195-202.
33. Fernandez C, Maradeix V, Gimenez F, Thuillier A, Farinotti R. Pharmacokinetics of zopiclone and its enantiomers in Caucasian young healthy volunteers. Drug Metab Dispos 1993; 21: 1125-1128.
34. Fernandez C, Gimenez F, Mayrargue J, Thuillier A, Farinotti R. Degradation and racemization of zopiclone enantiomers in plasma and partially aqueous solutions. Chirality 1995; 7: 267-271.
35. Fernandez C, Alet P, Davrinche C et al. Stereo-selective distribution and stereoconversion of zopiclone enantiomers in plasma and brain tissues in rats. J Pharm Pharmacol 2002; 54: 335-340.
36. McKernan RM, Rosahl TW, Reynolds DS et al. Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor a1 subtype. Nature Neurosci 2000; 3: 587-592.
37. Laven M, Markides K, Langstrom B. Analysis of microsomal metabolic stability using high-flow-rate extraction coupled to capillary liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 806: 119-126.