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The hypothalamic peptides orexin-A and orexin-B are potent agonists of two G-protein coupled receptors, namely the OX(1) and the OX(2) receptor. These receptors are widely distributed, though differentially, in the rat brain. In particular, the OX(1) receptor is highly expressed throughout the hypothalamus, whilst the OX(2) receptor is mainly located in the(More)
This study utilised the selective 5-ht(5A) receptor antagonist, SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), to investigate 5-ht5A receptor function in guinea pig brain. SB-699551-A competitively antagonised 5-HT-stimulated [35S]GTPgammaS binding to membranes(More)
The mechanisms through which blockade of metabotropic glutamate receptors 5 (mGluR5) results in anxiolytic and antidepressant effects are currently unknown. In the present study, we therefore hypothesized that the anxiolytic- and antidepressant-like profile of the noncompetitive mGluR5 receptor antagonist 2-ethyl-6-(phenylethynyl)-pyridine (MPEP) may be(More)
In this work the pharmacology and the receptor kinetics of the following orexin receptor antagonists SB-649868, ACT-078573, JNJ-10397049, MK-6096 and Roche-Cp were evaluated at human OX(1) and OX(2) orexin receptors by using functional and receptor binding assays. Kinetic analysis of the unlabeled ligands was carried out by indirect measurement according to(More)
5-{2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}-2(1H)-quinolinones and 3,4-dihydro-2(1H)-quinolinones have been identified with different combinations of 5-HT(1) autoreceptor antagonist and hSerT potencies and excellent rat PK profiles. The availability of tool compounds with a range of profiles at targets known to play a key role in the control of(More)
An increase in brain 5-HT levels is thought to be the key mechanism of action which results in an antidepressant response. It has been proven that selective serotonin re-uptake inhibitors are effective antidepressants but the delay to therapeutic onset of these agents is thought to be due to the time required for 5-HT1A, and possibly 5-HT1B, autoreceptor(More)
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