Benzodiazepine GABA-ionophore receptor complex ligands showed persistent modulation of the chloride ionophore, labeled by [(35)S]TBPS, even after receptor complex extensive purification. GABA caused inhibition of [(35)S]TBPS binding, while benzodiazepine agonists increased and benzodiazepine inverse agonists decreased the specific [(35)S]TBPS binding to the purified receptor. When GABA binding sites were occupied by the neurotransmitter benzodiazepine receptor agonists and antagonists reversed their effects clonazepam in fact inhibited and ?-carboline ethyl ester increased [(35)S]TBPS binding in the presence of GABA. The antagonist flumazenil showed no effect both in the presence or absence of GABA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/0197-0186(89)90153-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacological profile of essential oils derived from Lavandula angustifolia and Melissa officinalis with anti-agitation properties: focus on ligand-gated channels.
J Pharm Pharmacol
November 2008
Department of Pharmacology & Toxicology, University of Otago, PO Box 913, Dunedin, New Zealand.
Both Melissa officinalis (Mo) and Lavandula angustifolia (La) essential oils have putative anti-agitation properties in humans, indicating common components with a depressant action in the central nervous system. A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically validated essential oil derived from La, which has shown clinical benefit in treating agitation. La inhibited [35S] TBPS binding to the rat forebrain gamma aminobutyric acid (GABA)(A) receptor channel (apparent IC50 = 0.
View Article and Find Full Text PDFA ketogenic diet rescues the murine succinic semialdehyde dehydrogenase deficient phenotype.
Exp Neurol
April 2008
Program in Neuroscience and Mental Health, Hospital for Sick Children, and Department of Pharmacology, University of Toronto, Ontario, Canada.
Succinic semialdehyde dehydrogenase (SSADH) deficiency is a heritable disorder of GABA degradation characterized by ataxia, psychomotor retardation and seizures. To date, there is no effective treatment for SSADH deficiency. We tested the hypothesis that a ketogenic diet (KD) would improve outcome in an animal model of SSADH deficiency, the SSADH knockout mouse (Aldh5a1-/-).
View Article and Find Full Text PDFEnaminone amides as novel orally active GABAA receptor modulators.
J Med Chem
July 2007
Department of Pharmacology, School of Medicine, Med Surge 2, University of California-Irvine, Irvine, California 92697, USA.
A series of enaminone esters and amides have been developed as potent allosteric modulators of gamma-aminobutyric acidA (GABAA) receptors. The compounds bind to a novel modulatory site that is independent of the benzodiazepine (BZ), isosteric GABA, and neuroactive steroid binding sites. Structure-activity relationship (SAR) studies resulted in the synthesis of the c-Bu amide 16h with an in vitro potency of 7 nM based on inhibition of [35S]TBPS binding.
View Article and Find Full Text PDFCharacterization of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to GABAA receptors in postmortem human brain.
Br J Pharmacol
April 2007
Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, UK.
Background And Purpose: The aim of the present study was to determine whether binding of [(35)S]t-butylbicyclophosphorothionate ([(35)S]TBPS) to the convulsant binding site of GABA(A) receptors in human postmortem brain samples can be used as an in vitro index of the functional activation of these receptors.
Experimental Approach: Postmortem stability of [(35)S]TBPS binding was assessed in rat brain samples harvested at various times after death and the binding properties of [(35)S]TBPS binding (K(D) and B(max)) were determined in human postmortem brain using radioligand binding studies. In addition, the ability of human brain [(35)S]TBPS binding to be allosterically modulated by compounds that bind at recognition sites distinct from the convulsant binding site was measured.
Evidence for a reduction of coupling between GABAA receptor agonist and ionophore binding sites by inorganic phosphate.
Neurochem Res
December 2005
Institute of Biomedicine, Pharmacology, University of Helsinki, P.O.Box 63, Helsinki, FI-00014, Finland.
[35S]TBPS binding to the GABAA receptor ionophore binding site is anion dependent. Using autoradiography on rat brain sections, we show that permeabilities of anions through the receptor channel correlate with their efficiencies to promote basal [35S]TBPS binding. Phosphate made an exception as it induced more binding than expected from its permeability.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!