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dc.contributor.authorHudson, A.L.
dc.contributor.authorGough, R.
dc.contributor.authorTyacke, Robin
dc.contributor.authorLione, Lisa
dc.contributor.authorLalies, M.D.
dc.contributor.authorLewis, J.
dc.contributor.authorHusbands, S.
dc.contributor.authorKnight, P.
dc.contributor.authorMurray, F.
dc.contributor.authorHutson, P.
dc.contributor.authorNutt, D.J.
dc.date.accessioned2014-01-22T10:30:29Z
dc.date.available2014-01-22T10:30:29Z
dc.date.issued1999-06
dc.identifier.citationHudson , A L , Gough , R , Tyacke , R , Lione , L , Lalies , M D , Lewis , J , Husbands , S , Knight , P , Murray , F , Hutson , P & Nutt , D J 1999 , ' Novel selective compounds for the investigation of imidazoline receptors ' , Annals of the New York Academy of Sciences , vol. 881 , pp. 81-91 . https://doi.org/10.1111/j.1749-6632.1999.tb09344.x
dc.identifier.issn0077-8923
dc.identifier.otherPURE: 1491960
dc.identifier.otherPURE UUID: 546c8a7f-188b-4bdd-a642-07d2c1b2fa88
dc.identifier.otherScopus: 0032799471
dc.identifier.urihttp://hdl.handle.net/2299/12610
dc.description.abstractOver several years our group has sought to synthesize and identify selective ligands for imidazoline (I) receptors, in particular the I2 binding site. As a consequence, [3H]2-(2-benzofuranyl)-2-imidazoline (2BFI) has proved extremely useful for binding and autoradiographic studies. More recently we have synthesized a BU series of compounds and examined these for their affinities for both I1 and I2 binding sites. BU224 (2-(4,5-dihydroimidaz-2-yl)-quinoline) shows high affinity for I2 receptors with a Ki of 2.1 nM. BU226 (2-(4,5-dihydroimidaz-2-yl)-isoquinoline) demonstrated slightly higher affinity (Ki 1.4 nM) for I2 receptors, but overall BU224 displayed greater selectivity for I2 over I1 receptors (832-fold) than BU226 (380-fold). Both compounds showed low (μM) affinity for α2-adrenoceptors. Given BU224's ability to cross the blood brain barrier, we predict that its in vivo effects are likely to be mediated via I2 receptors. Brain dialysis revealed BU224 to dose dependently (0–20 mg/kg ip) elevate basal noradrenaline in rat frontal cortex and basal dopamine in striatum. In a rat model of opiate withdrawal, behavioral studies showed that BU224 (10 mg/kg, sc) was able to reduce acute weight loss and diarrhea, but not the number of wet dog shakes associated with the withdrawal syndromeen
dc.language.isoeng
dc.relation.ispartofAnnals of the New York Academy of Sciences
dc.titleNovel selective compounds for the investigation of imidazoline receptorsen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionCardiovascular Pathologies
dc.contributor.institutionDiabetic neuropathies
dc.contributor.institutionTRP Ion channels
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dcterms.dateAccepted1999-06
rioxxterms.versionofrecordhttps://doi.org/10.1111/j.1749-6632.1999.tb09344.x
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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