Benzodiazepine antagonist Ro 15-1788: Neurological and behavioral effects

Bonetti, E. P.; Pieri, L.; Cumin, R.; Schaffner, R.; Pieri, Margherita; Gamzu, Elkan; Müller, Rita; Haefely, W.

doi:10.1007/bf00470579

Cited by 334 publications

(95 citation statements)

References 19 publications

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“…In order to further characterize the type of receptor mediating the anorexigenic action of ODN and its analogs, in the present study we have investigated the effect of selective endozepine receptor antagonists on ODN, OP, and cOP-induced food consumption. The specific CBR antagonist flumazenil (Bonetti et al, 1982) and the specific PBR antagonist PK11195 (Le Fur et al, 1983) did not prevent the inhibitory effect of ODN, OP, and cOP on food intake. Conversely, cDLOP, which acts as a metabotropic endozepine receptor antagonist , suppressed the anorexigenic effect of ODN, OP, and cOP.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of the Receptor Mediating the Anorexigenic Action of the Octadecaneuropeptide: Evidence for an Endozepinergic Tone Regulating Food Intake

Rego

Orta

Leprince

et al. 2006

Neuropsychopharmacol

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Peptides of the endozepine family, including diazepam-binding inhibitor, the triakontatetraneuropeptide, and the octadecaneuropeptide (ODN), act through three types of receptors, that is, central-type benzodiazepine receptors (CBR), peripheral-type (mitochondrial) benzodiazepine receptors (PBR) and a metabotropic receptor positively coupled to phospholipase C via a pertussis toxin-sensitive G protein. We have previously reported that ODN exerts a potent anorexigenic effect in rat and we have found that the action of ODN is not affected by the mixed CBR/PBR agonist diazepam. In the present report, we have tested the possible involvement of the metabotropic receptor in the anorexigenic activity of ODN. Intracerebroventricular administration of the C-terminal octapeptide (OP) and its head-to-tail cyclic analog cyclo 1-8 OP (cOP) at a dose of 100 ng mimicked the inhibitory effect of ODN on food intake in fooddeprived mice. The specific CBR antagonist flumazenil and the PBR antagonist PK11195 did not prevent the effect of ODN, OP, and cOP on food consumption. In contrast, the selective metabotropic endozepine receptor antagonist cyclo 1-8 [DLeu 5 ]OP (100-1000 ng; cDLOP) suppressed the anorexigenic effect of ODN, OP, and cOP. At the highest concentration tested (1000 ng), cDLOP provoked by itself a significant increase in food intake. Taken together, the present results indicate that the anorexigenic effect of ODN and OP is mediated through activation of the metabotropic receptor recently characterized in astrocytes. The data also suggest that endogenous ODN, acting via this receptor, exerts an inhibitory tone on feeding behavior.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of the Receptor Mediating the Anorexigenic Action of the Octadecaneuropeptide: Evidence for an Endozepinergic Tone Regulating Food Intake

Rego

Orta

Leprince

et al. 2006

Neuropsychopharmacol

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“…SR95195, at low non-anxiogenic doses, also reversed the anticonflict action of diazepam. Again, inverse BZD agonists and BZD antagonists have repeatedly been shown to antagonize the anxiolytic effect of BZD ligands (Bonetti et al, 1982;Patel et al, 1983). SR95195, unlike CGS8216 (Mendelson et al, 1983) failed to counteract the disinhibitory effect of pentobarbitone in the approach-avoidance conflict test in rats, suggesting a greater selectivity towards the BZD receptor.…”

Section: Discussionmentioning

confidence: 99%

A 7‐phenyl substituted triazolopyridazine has inverse agonist activity at the benzodiazepine receptor site

Biziere

Bourguignon²,

Chambón

et al. 1987

British J Pharmacology

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1 To investigate further the structural requirements for benzodiazepine (BZD) receptor ligands, we synthesized SR.95195, [7-phenyl-3-methyl-1,2,4-triazolo-(4,3-b) pyridazine], a positional isomer of the 6-phenyl-triazolo-pyridazines, which were the first non-BZD derivatives to exhibit high affinity for the BZD receptor and BZD-like activity in vivo. (EDm: 8.6 mg kg-', i.p.), but not that of pentobarbitone 15 mg kg-', i.p.5 It is concluded that SR 95195 has the pharmacological profile of an inverse BZD agonist and that displacing the phenyl from the 6-to the 7-position in the triazolopyridazine series causes a shift from agonist to inverse agonist type activity at the BZD receptor site.

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“…according to a slight modification of the method reported by Bonetti et al (1982). Briefly, the mice were lifted by the tail and allowed to grasp a horizontally strung wire (1 mm diameter, 15 cm long and placed 20 cm above the table) with their forepaws, after which they were then released.…”

Section: Elevated Plus-maze Testmentioning

confidence: 99%

Anxiolytic-like effects of Portulaca oleraceae L. using the elevated plus-maze in mice

Lee¹,

Yoon²,

Ryu³

et al. 2009

Oriental Pharmacy and Experimental Medicine

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SUMMARYThe purpose of this study was to characterize the putative anxiolytic-like effects of the 70% ethanol extract of Portulaca oleracea (EPO) using an elevated plus maze (EPM) in mice. The EPO was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM, respectively. Control mice were treated with an equal volume of 10% tween 80, and positive control mice with diazepam (1 mg/kg). Single treatments of the EPO significantly increased the percentage of time spent and arm entries into the open arms of the EPM versus controls (P < 0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In addition, the anxiolyticlike effects of the EPO were blocked by flumazenil (10 mg/kg, i.p), a GABA receptor antagonist. These results indicate that P. oleracea is an effective anxiolytic agent, and suggest that the anxiolytic-like effects of P. oleracea is mediated via the GABAergic nervous system.

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Benzodiazepine antagonist Ro 15-1788: Neurological and behavioral effects

Cited by 334 publications

References 19 publications

Pharmacological Characterization of the Receptor Mediating the Anorexigenic Action of the Octadecaneuropeptide: Evidence for an Endozepinergic Tone Regulating Food Intake

Pharmacological Characterization of the Receptor Mediating the Anorexigenic Action of the Octadecaneuropeptide: Evidence for an Endozepinergic Tone Regulating Food Intake

A 7‐phenyl substituted triazolopyridazine has inverse agonist activity at the benzodiazepine receptor site

Anxiolytic-like effects of Portulaca oleraceae L. using the elevated plus-maze in mice

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