[3H]RP 62203, a ligand of choice to label in vivo brain 5-HT2 receptors.
There are only a few ligands available for labelling brain receptors simply because in vivo binding requires more severe experimental conditions than in vitro binding. We now describe the in vivo binding properties of [3H]RP 62203, a new potent and selective 5-HT2 antagonist. After intravenous injection into rats, [3H]RP 62203 accumulated predominantly in brain regions containing 5-HT2 receptors, with a frontal cortex/cerebellum ratio of 6 to 7. A good correlation was obtained between the regional distribution of [3H]RP 62203 in the brain and the density of 5-HT2 receptors measured in vitro. In vivo binding of [3H] RP 62203 was saturable in the frontal cortex but not in the cerebellum. The Bmax in the frontal cortex was equal to 42.5 fmol/mg, thus in the same range as was found in vitro. The 5-HT2 selectivity was ascertained by displacement (prevention) experiments; 5-HT2 antagonists or the agonist 2,5-dimethoxy- 4-iodophenylisopropylamine could prevent specific labelling of [3H]RP 62203 only in brain regions containing 5-HT2 receptors. Interestingly, the radioactivity remaining in various brain regions after displacement with pipamperone corresponded exactly to that measured in the cerebellum, with or without pipamperone. In conclusion, [3H]RP 62203 possesses striking properties of in vivo binding which make it a suitable candidate for examining 5-HT2 receptors in human brain by positron emission tomography scanning.
Fajolles
C
C
Centre de Recherches Rhône-Poulenc Rorer, Vitry sur Seine, France.
Boireau
A
A
Ponchant
M
M
Laduron
P M
PM
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002090:Butyrophenones / Q000494:pharmacology; D003499:Cyclic S-Oxides / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D008297:Male; D009281:Naphthalenes / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology
D000662:Amphetamines; D002090:Butyrophenones; D003499:Cyclic S-Oxides; D008024:Ligands; D009281:Naphthalenes; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; C070475:fananserin; C005569:pipamperone; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine