Quantification of in vivo binding of [3H]RX 821002 in rat brain: evaluation as a radioligand for central alpha 2-adrenoceptors.
On the basis of its established in vitro characteristics, [3H]RX 821002 was evaluated in rats as an in vivo radioligand for central alpha 2-adrenoceptors. Estimates for in vivo binding potential, obtained by compartmental analyses of time-radioactivity data, ranged between 1.9 for hypothalamus and 0.2 for cerebellum, with a regional distribution in brain which was similar to that observed in vitro. Selectivity and specificity of the signal were checked by predosing with either the alpha 2-antagonists, idazoxan or yohimbine, the alpha 2-agonist, clonidine, or the alpha 1-antagonist, prazosin. Pretreatment of the rats with the selective neurotoxin, DSP-4, had no significant effect on [3H]RX 821002 binding, suggesting that the majority of labelled sites were situated post-junctionally. The studies indicate that [3H]RX 821002 can be used experimentally as an in vivo marker for central alpha 2-adrenoceptors. The size and rate of expression of the specific signal encourage the development and assessment of [11C]RX 821002 for clinical PET studies.
Hume
S P
SP
MRC Cyclotron Unit, Hammersmith Hospital, London, England.
Lammertsma
A A
AA
Opacka-Juffry
J
J
Ahier
R G
RG
Myers
R
R
Cremer
J E
JE
Hudson
A L
AL
Nutt
D J
DJ
Pike
V W
VW
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004146:Dioxanes / Q000378:metabolism* / Q000494:pharmacology; D019329:Idazoxan / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; C058525:2-methoxyidazoxan; D019329:Idazoxan