Evaluation of a rapid technique for detecting minor tranquilizers

Aron, C; Simon, Pierre; Larousse, C; Boissier, J R

doi:10.1016/0028-3908(71)90074-8

Cited by 159 publications

(47 citation statements)

References 8 publications

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“…Four-plate testing (FPT), based on the method of Aron et al (1971), consisted of a nontransparent Plexiglas box (25 ϫ 18 ϫ 16 cm) with a transparent lid constructed at NeuroSearch A/S (Bellerup, Denmark). The floor of the chamber consisted of four identical rectangular metal plates (11 ϫ 8 cm), which were separated by a 4-mm gap and through which an electric foot shock (0.6 mA; 0.5 s) could be delivered manually using a foot pedal (BioSeb, Vitrolles, France).…”

Section: Four-plate Testingmentioning

confidence: 99%

NS11394 [3′-[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a Unique Subtype-Selective GABA_A Receptor Positive Allosteric Modulator: In Vitro Actions, Pharmacokinetic Properties and in Vivo Anxiolytic Efficacy

Mirza

Larsen²,

Mathiasen³

et al. 2008

J Pharmacol Exp Ther

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The novel positive allosteric modulator NS11394 [3Ј-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile] possesses a functional selectivity profile at GABA A receptors of ␣ 5 Ͼ ␣ 3 Ͼ ␣ 2 Ͼ ␣ 1 based on oocyte electrophysiology with human GABA A receptors. Compared with other subtype-selective ligands, NS11394 is unique in having superior efficacy at GABA A -␣ 3 receptors while maintaining low efficacy at GABA A -␣ 1 receptors. NS11394 has an excellent pharmacokinetic profile, which correlates with pharmacodynamic endpoints (CNS receptor occupancy), yielding a high level of confidence in deriving in vivo conclusions anchored to an in vitro selectivity profile and allowing for translation to higher species. Specifically, we show that NS11394 is potent and highly effective in rodent anxiety models. The anxiolytic efficacy of NS11394 is most probably mediated through its high efficacy at GABA A -␣ 3 receptors, although a contributory role of GABA A -␣ 2 receptors cannot be excluded. Compared with benzodiazepines, NS11394 has a significantly reduced side effect profile in rat (sedation, ataxia, and ethanol interaction) and mouse (sedation), even at full CNS receptor occupancy. We attribute this benign side effect profile to very low efficacy of NS11394 at GABA A -␣ 1 receptors and an overall partial agonist profile across receptor subtypes. However, NS11394 impairs memory in both rats and mice, which is possibly attributable to its efficacy at GABA A -␣ 5 receptors, albeit activity at this receptor might be relevant to its antinociceptive effects (J Pharmacol Exp Ther 327:doi;10.1124/jpet.108.144, 2008). In conclusion, NS11394 has a unique subtype-selective GABA A receptor profile and represents an excellent pharmacological tool to further our understanding on the relative contributions of GABA A receptor subtypes in various therapeutic areas.Preclinical studies using genetically modified mice suggest that GABA A -␣ 1 (Rudolph et al., 1999;McKernan et al., 2000), ␣ 2 (Low et al., 2000), and ␣ 5 (Collinson et al., 2002;Crestani et al., 2002)-containing receptors mediate the sedative/ motor-impairing, anxiolytic, and memory impairing effects of benzodiazepines, respectively. Pharmacologically, various nonbenzodiazepine compounds have been described that show either selective affinity (e.g., zolpidem and indiplon) or selective efficacy (e.g., L-838,417, SL651498, TP003, TPA023) for subtypes of GABA A receptors (Sanger et al., 1987;McKernan et al., 2000;Griebel et al., 2001;Dias et al., 2005;Atack et al., 2006). Such selectivity profiles have been argued to be the basis for selective behavioral profiles of these compounds in rodents and in some cases man. For example, zolpidem is selective for GABA A -␣ 1 -containing receptors, has a preferential sedative-hypnotic profile in animals, and is marketed as a sleep aid zolpidem tartrate (Ambien). Although additional compounds with various selectivity profiles have emerged, limited clinical data in patient populations exist to date (but see Basile...

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Section: Four-plate Testingmentioning

confidence: 99%

NS11394 [3′-[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a Unique Subtype-Selective GABA_A Receptor Positive Allosteric Modulator: In Vitro Actions, Pharmacokinetic Properties and in Vivo Anxiolytic Efficacy

Mirza

Larsen²,

Mathiasen³

et al. 2008

J Pharmacol Exp Ther

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“…Experimental sessions are 1 min in length and the number of punished crossings is recorded by a computer attached to the shocker device. Clinically effective classes of anxiolytic compounds such as benzodiazepines, selective serotonin reuptake inhibitors, or partial 5-HT 1A agonists produce increases in punished crossings, which is indicative of anxiolytic-like activity (Aron et al, 1971;Bourin et al, 1992;Hascoet et al, 2000).…”

Section: Four-plate Testmentioning

confidence: 99%

Increasing the Levels of Insulin-Like Growth Factor-I by an IGF Binding Protein Inhibitor Produces Anxiolytic and Antidepressant-Like Effects

Malberg

Platt

Rizzo

et al. 2007

Neuropsychopharmacol

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The present studies were conducted to determine if increasing central levels of the neurotrophic factor insulin-like growth factor-1 (IGF-I) either directly or indirectly produces anxiolytic and antidepressant-like effects in the mouse. Central levels of IGF-I can be increased directly, by administering IGF-I, or indirectly by blocking the insulin-like growth factor binding proteins (IGFBPs). The IGFBP family has the unique ability to regulate IGF-I levels by sequestering IGF-I into an inactive complex. Therefore, an IGFBP inhibitor increases the level of IGF-I available to bind to its receptor. Intracerebroventricular (icv) administration of the nonspecific IGFBP inhibitor NBI-31772 (10-30 mg) increases the number of punished crossings in the four-plate test and NBI-31772 (0.3-10 mg) increases time spent in the open quadrant of the elevated zero maze (EZM), indicative of anxiolytic-like effects. NBI-31772 (3-30 mg) also decreases immobility time in the tail suspension test, indicative of antidepressant-like effects. Similarly, icv administration of IGF-I (0.1 mg) produces anxiolytic-like effects in the four-plate test and IGF-1 (0.3-1 mg ) produces anxiolytic-like effects in the EZM. IGF-I (10 mg) also produces antidepressantlike effects in the tail suspension test. Coadministration of the IGF-I receptor antagonist JB1 with NBI-31772 or IGF-I blocks the anxiolyticlike and antidepressant-like effects of these compounds. These results suggest that NBI-31772 produces behavioral effects by increasing levels of IGF-I that in turn activate the IGF-I receptor. The present studies demonstrate that an IGFBP inhibitor mimics the behavioral effects of IGF-I and that IGFBP inhibition may represent a novel mechanism by which to increase IGF-I to treat depression and anxiety.

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“…Calming and exploratory behavior were used as parameters of anxiety level (Depino et al, 2008;Aron et al, 1971). The elevated plus maze test is used to evaluate anxiety-related behaviors and it involves a conflict between the rodent's desire to explore a novel environment and anxiogenic elements, such as elevation and an unfamiliar, brightly illuminated area (Lister, 1987).…”

Section: Discussionmentioning

confidence: 99%

Psychopharmacological Profile of the Water Extract of Gardenia jasminoides and Its Constituents, Genipin and Geniposide, in Mice

Choi¹,

Peña²,

Choi³

et al. 2008

Biomolecules and Therapeutics

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− Gardenia jasminoides (G. jasminoides) is traditionally used to treat insomnia, jaundice, emotional disorders, hepatic disease, and inflammatory disease. Previously, we found that geniposide and the water extract of G. jasminoides increased Cl -influx in neuroblastoma. Here we examined the psychopharmacological activities of G. jasminoides and its constituents. G. jasminoides extract was orally administered at 100 and 200 mg/kg, and genipin and geniposide were intraperitoneally injected at 2, 10, and 20 mg/kg. Electroshock stress decreased open arm activity, but the extract and geniposide (20 mg/kg) significantly reversed that effect. This results indicate that G. jasminoides extract and geniposide alleviated anxiety with greater efficacy in stressed animals than normal animals.

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Evaluation of a rapid technique for detecting minor tranquilizers

Cited by 159 publications

References 8 publications

NS11394 [3′-[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a Unique Subtype-Selective GABA_A Receptor Positive Allosteric Modulator: In Vitro Actions, Pharmacokinetic Properties and in Vivo Anxiolytic Efficacy

NS11394 [3′-[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a Unique Subtype-Selective GABA_A Receptor Positive Allosteric Modulator: In Vitro Actions, Pharmacokinetic Properties and in Vivo Anxiolytic Efficacy

Increasing the Levels of Insulin-Like Growth Factor-I by an IGF Binding Protein Inhibitor Produces Anxiolytic and Antidepressant-Like Effects

Psychopharmacological Profile of the Water Extract of Gardenia jasminoides and Its Constituents, Genipin and Geniposide, in Mice

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Evaluation of a rapid technique for detecting minor tranquilizers

Cited by 159 publications

References 8 publications

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

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

Increasing the Levels of Insulin-Like Growth Factor-I by an IGF Binding Protein Inhibitor Produces Anxiolytic and Antidepressant-Like Effects

Psychopharmacological Profile of the Water Extract of Gardenia jasminoides and Its Constituents, Genipin and Geniposide, in Mice

Contact Info

Product

Resources

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NS11394 [3′-[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a Unique Subtype-Selective GABA_A Receptor Positive Allosteric Modulator: In Vitro Actions, Pharmacokinetic Properties and in Vivo Anxiolytic Efficacy

NS11394 [3′-[5-(1-Hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2-carbonitrile], a Unique Subtype-Selective GABA_A Receptor Positive Allosteric Modulator: In Vitro Actions, Pharmacokinetic Properties and in Vivo Anxiolytic Efficacy