3
28
Journal of Psychopharmacology 25(3)
benzodiazepine site of GABA
enhancing properties. J Med Chem 47: 5829–5832.
A
a5 receptors with cognition
A
Maubach KA (2003) GABA receptor subtype selective cognition
enhancers. Curr Drug Targets CNS Neurol Disord 2: 233–239.
Mirza NR, Larsen JS, Mathiasen C, et al. (2008) NS11394 [3’-[5-
(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-car-
Dawson GR, Tricklebank MD (1995) Use of the elevated plus maze
in the search for novel anxiolytic agents. Trends Pharmacol Sci 16:
3
3–36.
Dawson GR, Curnow R, Bayley P, Rambridge A, Tricklebank MD
1994) Lack of effect of flumazenil and CGS 8216 on the
anxiolytic-like properties of loreclezole. Eur J Pharmacol 252:
25–328.
Dawson GR, Maubach KA, Collinson N, et al. (2006) An inverse
agonist selective for a5 subunit-containing GABA receptors
A
bonitrile], a unique subtype-selective GABA receptor positive
allosteric modulator: in vitro actions, pharmacokinetic properties
and in vivo anxiolytic efficacy. J Pharmacol Exp Ther 327:
954–968.
(
3
Morris HV, Dawson GR, Reynolds DS, Atack JR, Stephens DN
(2006) Both a2 and a3 GABA
anxiolytic properties of benzodiazepine site ligands in the condi-
tioned emotional response paradigm. Eur Neurosci 23:
495–2504.
Munro G, Lopez-Garcia JA, Rivera-Arconada I, et al. (2008)
Comparison of the novel subtype-selective GABA
A
A
receptor subtypes mediate the
A
J
enhances cognition. J Pharmacol Exp Ther 316: 1335–1345.
De Haas SL, de Visser SJ, van der Post JP, et al. (2007)
Pharmacodynamic and pharmacokinetic effects of TPA023, a
2
GABA
and placebo in healthy volunteers.
74–383.
A
a2,3 subtype-selective agonist, compared to lorazepam
receptor-positive allosteric modulator NS11394 [3’-[5-(1-
hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-
J
Psychopharmacol 21:
3
biphenyl-2-carbonitrile] with diazepam, zolpidem, bretazenil, and
gaboxadol in rat models of inflammatory and neuropathic pain.
J Pharmacol Exp Ther 327: 969–981.
De Haas SL, de Visser SJ, van der Post JP, et al. (2008)
Pharmacodynamic and pharmacokinetic effects of MK-0343, a
GABA
and placebo in healthy male volunteers. J Psychopharmacol 22:
4–32.
De Haas SL, Franson KL, Schmitt JAJ, et al. (2009) The pharma-
cokinetic and pharmacodynamic effects of SL65.1498, a GABA
2,3 selective agonist, in comparison with lorazepam in healthy
volunteers. J Psychopharmacol 23: 625–632.
A
a2,3 subtype selective agonist, compared to lorazepam
Popik P, Kostakis E, Krawczyk M, et al. (2006) The
anxioselective agent 7-(2-chloropyridin-4-yl)pyrazolo-[1,5-a]-pyri-
midin-3-yl](pyridin-2-yl)methanone (DOV 51892) is more effica-
2
cious than diazepam at enhancing GABA-gated currents at a
subunit-containing GABA receptors. J Pharmacol Exp Ther
19: 1244–1252.
Rowlett JK, Platt DM, Lelas S, Atack JR, Dawson GR (2005)
Different GABA receptor subtypes mediate the anxiolytic,
1
A
A
a
3
De Visser SJ, van der Post JP, de Waal PP, Cornet F, Cohen AF, van
Gerven JMA (2003) Biomarkers for the effects of benzodiazepines
in healthy volunteers. Br J Clin Pharmacol 55: 39–50.
A
abuse-related, and motor effects of benzodiazepine-like drugs in
primates. Proc Natl Acad Sci USA 102: 915–920.
Dias R, Sheppard WFA, Fradley RL, et al. (2005) Evidence for a
¨
A
Rudolph U, Mohler H (2004) Analysis of GABA receptor function
significant role of a3-containing GABA
the anxiolytic effects of benzodiazepines.
0682–10688.
A
receptors in mediating
and dissection of the pharmacology of benzodiazepines and gen-
eral anesthetics through mouse genetics. Annu Rev Pharmacol
Toxicol 44: 475–498.
J
Neurosci 25:
1
Griebel G, Perrault G, Simiand J, et al. (2001) SL651498: An anxio-
selective compound with functional selectivity for a2- and
Rudolph U, Crestani F, Benke D, et al. (1999) Benzodiazepine
actions mediated by specific g-aminobutyric acid
types. Nature 401: 796–800.
A
receptor sub-
a3-containing g-aminobutyric acid
J Pharmacol Exp Ther 298: 753–768.
A
(GABA
A
)
receptors.
Salmi E, Aalto S, Hirvonen J, et al. (2008) Measurement of GABA
A
Hadingham KL, Garrett EM, Wafford, KA, et al. (1996) Cloning of
cDNAs encoding the human g-aminobutyric acid type A receptor
a6 subunit and characterization of the pharmacology of
a6-containing receptors. Mol Pharmacol 49: 253–259.
Hadingham KL, Wingrove P, Le Bourdelles B, Palmer KJ, Ragan
CI, Whiting PJ (1993) Cloning of cDNA sequences encoding
11
receptor binding in vivo with [ C]Flumazenil: a test-retest study
in healthy subjects. Neuroimage 41: 260–269.
¨
A
Savic MM, Huang S, Furtmuller R, et al. (2008) Are GABA recep-
´
tors containing a5 subunits contributing to the sedative properties
of benzodiazepine site agonists? Neuropsychopharmacology 33:
332–339.
Sieghart W (2006) Structure, pharmacology, and function of GABA
receptor subtypes. Adv Pharmacol 54: 231–263.
A
human a2 and a3 g-aminobutyric acid receptor subunits and
A
characterization of the benzodiazepine pharmacology of recombi-
nant a1-, a2-, a3-, and a5-containing human g-aminobutyric
acid receptors. Mol Pharmacol 43: 970–975.
A
Sieghart W, Sperk G (2002) Subunit composition, distribution and
function of GABA receptor subtypes. Curr Top Med Chem 2:
95–816.
Simon J, Wakimoto H, Fujita N, Lalande M, Barnard EA (2004)
Analysis of the set of GABA receptor genes in the human
genome. J Biol Chem 279: 41422–41435.
Van Laere K, Bormans G, Sanabria-Bohorquez SM, et al. (2008) In
A
Krause JE, Matchett M, Crandall M, Yu J, Baltazar C, Brodbeck
RM, Kehne JH, Maynard GD, Shaw KR, Chenard BL,
Hutchison AJ, Xie L and Yu W (2007) I. Preclinical characteriza-
tion in vitro of NG2-73 as a potent and selective partial allosteric
7
A
A
activator of GABA receptors with predominant efficacy at the
´
a3 subunit. Program No. AAA26. 2007 Neuroscience Meeting
Planner. San Diego, CA: Society for Neuroscience, 2007. Online.
Lippa A, Czobor P, Stark J, et al. (2005) Selective anxiolysis pro-
vivo characterization and dynamic receptor occupancy imaging of
TPA023B, an a2/a3/a5 subtype selective g-aminobutyric acid-A
partial agonist. Biol Psychiatry 64: 153–161.
duced by ocinaplon, a GABA
Acad Sci USA 102: 7380–7385.
A
receptor modulator. Proc Natl
Van Steveninck AL, Gieschke R, Schoemaker RC, et al. (1996)
Pharmacokinetic and pharmacodynamic interactions of bretazenil
and diazepam with alcohol. Br J Clin Pharmacol 41: 565–573.
Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS,
Whiting PJ (1996) Functional characterization of human
g-aminobutyric acidA receptors containing the a4 subunit.
Mol Pharmacol 50: 670–678.
Low K, Crestani F, Keist R, et al. (2000) Molecular and neuronal
substrate for the selective attenuation of anxiety. Science 290:
¨
131–134.
McKernan RM, Whiting PJ (1996) Which GABA
A
-receptor subtypes
really occur in the brain? Trends Neurosci 19: 139–143.
McKernan RM, Rosahl TW, Reynolds DS, et al. (2000) Sedative but
not anxiolytic properties of benzodiazepines are mediated by the
¨
Wieland HA, Luddens H, Seeburg PH (1992) A single histidine in
GABAA receptors is essential for benzodiazepine agonist binding.
J Biol Chem 267: 1426–1429.
GABA
A
receptor a1 subtype. Nature Neurosci 3: 587–592.