NS11394 [3′-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]- biphenyl-2-carbonitrile], a unique subtype-selective GABAA receptor positive allosteric modulator: In vitro actions, pharmacokinetic properties and in vivo anxiolytic efficacy

Journal of Pharmacology and Experimental Therapeutics

Volumn 327, Issue 3, 2008, Pages 954-968

  Mirza, Naheed D ^a   Larsen, J S ^a   Mathiasen, C ^a   Jacobsen, T A ^a   Munro, G ^a   Erichsen, H K ^a   Nielsen, A N ^a   Troelsen, K B ^a   Nielsen, E O ^a   Ahring, P K ^a  

^a NEUROSEARCH A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

3' [5 (1 HYDROXY 1 METHYLETHYL)BENZOIMIDAZOL 1 YL]BIPHENYL 2 CARBONITRILE; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR STIMULATING AGENT; 8 AZIDO 5,6 DIHYDRO 5 METHYL 6 OXO 4H IMIDAZO[1,5 A][1,4]BENZODIAZEPINE 3 CARBOXYLIC ACID ETHYL ESTER; ANXIOLYTIC AGENT; BENZODIAZEPINE; CLONAZEPAM; DIAZEPAM; FLUNITRAZEPAM; GABA A ALPHA1 RECEPTOR; GABA A ALPHA3 RECEPTOR; GABA A ALPHA5 RECEPTOR; NS 11394; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG; ZOLPIDEM; 3' (5 (1 HYDROXY 1 METHYLETHYL)BENZOIMIDAZOL 1 YL)BIPHENYL 2 CARBONITRILE; 3'-(5-(1-HYDROXY-1-METHYLETHYL)BENZOIMIDAZOL-1-YL)BIPHENYL-2-CARBONITRILE; BENZIMIDAZOLE DERIVATIVE; LIGAND;

4 AMINOBUTYRIC ACID RELEASE; ALLOSTERISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINOCICEPTION; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SELECTIVITY; FEMALE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; MOLECULAR CLONING; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; RECEPTOR OCCUPANCY; TRANQUILIZING ACTIVITY; XENOPUS LAEVIS; ANIMAL; ANXIETY; DRUG EFFECT; DRUG POTENTIATION; MEMORY; PHARMACOKINETICS;

ALLOSTERIC REGULATION; ANIMALS; ANTI-ANXIETY AGENTS; ANXIETY; BENZIMIDAZOLES; HUMANS; LIGANDS; MEMORY; MICE; PHARMACOKINETICS; RATS; RECEPTORS, GABA-A;

EID: 57349185677     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.108.138859     Document Type: Article

References (34)

1. Aron C, Simon P, Larousse C, and Boissier JR (1971) Evaluation of a rapid technique for detecting minor tranquilizers. Neuropharmacology 10:459-469.
2. Atack JR (2003) Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. Curr Drug Targets CNS Neurol Disord 2:213-232.
3. A receptors. Br J Pharmacol 144:357-366.
4. A receptors, is a nonsedating anxiolytic in rodents and primates. J Pharmacol Exp Ther 316:410-422.
5. A receptor modulators as anxioselective anxiolytics. Drug Discov Today Therap Strat 3:475-481.
6. Broekkamp CL, Rijk HW, Joly-Gelouin D, and Lloyd KL (1986) Major tranquillizers can be distinguished from minor tranquillizers on the basis of effects on marble burying and swim-induced grooming in mice. Eur J Pharmacol 126:223-229.
7. Chouinard G (2004) Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 65 (Suppl 5):7-12.
8. A receptor. J Neurosci 22:5572-5580.
9. Crestani F, Keist R, Fritschy JM, Benke D, Vogt K, Prut L, Blüthmann H, Möhler H, and Rudolph U (2002) Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors. Proc Natl Acad Sci U S A 99:8980-8985.
10. de Haas SL, de Visser SJ, van der Post JP, de Smet M, Schoemaker RC, Rijnbeek B, Cohen AF, Vega JM, Agrawal NG, Goel TV, et al. (2007) Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers. J Psychopharmacol 21:374-383.
11. A receptors in mediating the anxiolytic effects of benzodiazepines. J Neurosci 25:10682-10688.
12. Ebert B, Wafford KA, and Deacon S (2006) Treating insomnia: current and investigational pharmacological approaches. Pharmacol Ther 112:612-629.
13. Griebel G, Perrault G, Tan S, Schoemaker H, and Sanger DJ (1999a) Comparison of the pharmacological properties of classical and novel BZ-omega receptor ligands. Behav Pharmacol 10:483-495.
14. Griebel G, Perrault G, and Sanger DJ (1999b) Study of the modulatory activity of BZ (omega) receptor ligands on defensive behaviors in mice: evaluation of the importance of intrinsic efficacy and receptor subtype selectivity. Prog Neuropsychopharmacol Biol Psychiatry 23:81-98.
15. A (GABA(A)) receptors. J Pharmacol Exp Ther 298:753-768.
16. Haefely W, Martin JR, and Schoch P (1990) Novel anxiolytics that act as partial agonists at benzodiazepine receptors. Trends Pharmacol Sci 11:452-456.
17. A/ benzodiazepine receptor subtypes: binding affinities of substituted beta-carbolines at recombinant alpha x beta 3 gamma 2 subtypes and quantitative structure-activity relationship studies via a comparative molecular field analysis. Drug Des Discov 16:55-76.
18. A receptor. J Biol Chem 277:41438-41447.
19. Knabl J, Witschi R, Hosl K, Reinold H, Zeilhofer UB, Ahmadi S, Brockhaus J, Sergejeva M, Hess A, Brune K, et al. (2008) Reversal of pathological pain through specific spinal GABAA receptor subtypes. Nature 451:330-334.
20. Löw K, Crestani F, Keist R, Benke D, Brünig I, Benson JA, Fritschy JM, Rülicke T, Bluethmann H, Mohler H, et al. (2000) Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290:131-134.
21. Mathiasen LS, Rodgers RJ, and Mirza NR (2007) Comparative effects of nonselective and subtype-selective gamma-aminobutyric acidA receptor positive modulators in the rat-conditioned emotional response test. Behav Pharmacol 18:191-203.
22. Maubach K (2003) GABA(A) receptor subtype selective cognition enhancers. Curr Drug Targets CNS Neurol Disord 2:233-239.
23. McKernan RM, Rosahl TW, Reynolds DS, Sur C, Wafford KA, Atack JR, Farrar S, Myers J, Cook G, Ferris P, et al. (2000) Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype. Nat Neurosci 3:587-592.
24. Mirza NR and Nielsen EØ (2006) Do subtype-selective gamma-aminobutyric acid A receptor modulators have a reduced propensity to induce physical dependence in mice? J Pharmacol Exp Ther 316:1378-1385.
25. A receptor-positive allosteric modulator NS11394 [3′-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2- carbonitrile] with diazepam, zolpidem, bretazenil, and gaboxadol in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther 327:969-981.
26. Nutt DJ, Besson M, Wilson SJ, Dawson GR, and Lingford-Hughes AR (2007) Blockade of alcohol's amnestic activity in humans by an alpha5 subtype benzodiazepine receptor inverse agonist. Neuropharmacology 53:810-820.
27. Paronis CA, Cox ED, Cook JM, and Bergman J (2001) Different types of GABA(A) receptors may mediate the anticonflict and response rate-decreasing effects of zaleplon, zolpidem, and midazolam in squirrel monkeys. Psychopharmacology (Berl) 156:461-468.
28. A receptor subtypes: an in vivo approach to exploring the therapeutic and side effects of benzodiazepine-type drugs. CNS Spectr 10:40-48.
29. Rudolph U, Crestani F, Benke D, Brünig I, Benson JA, Fritschy JM, Martin JR, Bluethmann H, and Möhler H (1999) Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes. Nature 401:796-800.
30. Sanger DJ, Perrault G, Morel E, Joly D, and Zivkovic B (1987) The behavioral profile of zolpidem, a novel hypnotic drug of imidazopyridine structure. Physiol Behav 41:235-240.
31. Scott-Stevens P, Atack JR, Sohal B, and Worboys P (2005) Rodent pharmacokinetics and receptor occupancy of the GABAA receptor subtype selective benzodiazepine site ligand L-838417. Biopharm Drug Dispos 26:13-20.
32. Shannon HE, Guzman F, and Cook JM (1984) beta-Carboline-3-carboxylate- t-butyl ester: a selective BZ1 benzodiazepine receptor antagonist. Life Sci 35:2227-2236.
33. Sieghart W (1995) Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes. Pharmacol Rev 47:181-234.
34. Van Bogaert M, Oosting R, Toth M, Groenink L, van Oorschot R, and Olivier B (2006) Effects of genetic background and null mutation of 5-HT1A receptors on basal and stress-induced body temperature: modulation by serotonergic and GABAA-ergic drugs. Eur J Pharmacol 550:84-90.