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Since the demonstration that serotonin (5-hydroxytryptamine, 5-HT) interacts with different (sub)types of membrane receptors, several compounds have been proposed as potent and selective ligands for one of these 5-HT subtypes. Unfortunately, specific and highly selective ligands (selectivity ratios greater than or equal to 1000) for the majority of 5-HT(More)
An overview is presented on progress made in research on 5-HT1A receptors and their ligands since their discovery in 1983. Molecular biology has offered new tools, for example cloned 5-HT1A receptors, their mutants and chimeras to study structure and function. Many compounds, belonging to different chemical classes, display high affinity and selectivity for(More)
Structure-affinity relationship (SAR) studies for 5-HT1A receptor site are presented for two series of heterobicyclic phenylpiperazines with N4-alkyl substituents: 4-alkyl derivatives of 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine (3) and 1-(benzo[b]furan-7-yl)piperazine (4). The linear and branched hydrocarbon chain derivatives up to n-decyl were(More)
Allosteric modulation of G protein-coupled receptors has recently been recognized as an alternative approach to gain selectivity in drug action. In this overview, allosteric modulators that enhance or diminish the effects of (endogenous) agonists or antagonists on a variety of G protein-coupled receptors are described. Emphasis is placed on the latest(More)
The present paper reviews the evidence for anxiolytic activity of 5-HT(3) receptor antagonists in animal models of anxiety and in clinical trials in humans. Compared to the established anxiolytics (benzodiazepine receptor agonists and, to a lesser extent, 5-HT(1A) receptor agonists) 5-HT(3) receptor antagonists display a different anxiolytic profile. They(More)
GABA is the major inhibitory neurotransmitter in the brain and GABA re- uptake from the synaptic cleft is one important mechanism in the regulation of GABA activity. Inhibition of the re-uptake of GABA by potent and selective inhibitors of the GABA transporter enhances GABA activity. This property can be used therapeutically in for instance epilepsy or(More)
Allosteric modulation of G protein-coupled receptors has recently been recognized as an alternative approach for selectivity in drug action. Allosteric modulators that enhance or diminish the effects of (endogenous) agonists or antagonists on a variety of G protein-coupled receptors are described in this review, with emphasis on the latest developments in(More)
The purpose of the present study was to quantify the in vivo potency of the selective adenosine A2a antagonist CSC [8-(3-chlorostyryl)caffeine]. Four groups of conscious, normotensive rats received a continuous i.v. infusion of 0, 6, 12 and 24 micrograms/min/kg of CSC. During a steady-state infusion of CSC, the animals received 1000 micrograms/kg of the(More)