title: Evaluation in rat of RS-79948-197 as a potential PET ligand for central alpha 2-adrenoceptors.
abstract: Tritium-labelled RS-79948-197 {(8aR,12aS,13aS)-5, 8,8a,9,10,11,12,12a,13,13a-decahydro-3-methoxy-12-(ethylsulphon yl)-6H-iso- quino[2,1-g][1,6]naphthyridine} was evaluated in rat brain as an in vivo ligand for central alpha 2-adrenoceptors, as a preliminary step in the development of a radioligand for positron-emission tomography (PET) studies. The maximal receptor-specific signal was achieved within 90-120 min after i.v. injection of [ethyl-3H]RS-79948-197 and was selective for the alpha 2- compared with the alpha 1-adrenoceptor, with no detectable binding to the imidazoline-I2 site. Estimates for binding potential (approximating to Bmax/Kd) ranged between 3.4 in entorhinal cortex and 0.5 in medulla oblongata. The results, which indicate a similarly localised but 2-fold increase in specific binding compared with that previously demonstrated using [3H]RX 821002 (2-methoxy-idazoxan), are sufficiently encouraging as to support further investment in the development of 11C-labelled RS-79948-197, or a close structural analogue, as a ligand for clinical PET.
authors.affiliation: PET Methodology Group, Cyclotron Unit, MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Hume
authors.forename: S
authors.initials: S
authors.lastname: Ashworth
authors.forename: A A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: J
authors.initials: J
authors.lastname: Opacka-Juffry
authors.forename: M P
authors.initials: MP
authors.lastname: Law
authors.forename: J A
authors.initials: JA
authors.lastname: McCarron
authors.forename: R D
authors.initials: RD
authors.lastname: Clark
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: V W
authors.initials: VW
authors.lastname: Pike
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D054755:Imidazoline Receptors; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000493:pharmacokinetics; D008024:Ligands; D008297:Male; D009287:Naphthyridines / Q000493:pharmacokinetics; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D054755:Imidazoline Receptors; D007546:Isoquinolines; D008024:Ligands; D009287:Naphthyridines; D010879:Piperazines; D011725:Pyridines; C104875:RS 79948-197; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide