Masakazu Fujio

Synthesis and evaluation of 11C-labeled (S)-N-{[1-(2-phenylethyl) pyrrolidin-2-yl]methyl}-3-methylthiobenzamide as a PET 5-HT1A receptor ligand

Abstract We prepared 5-HT 1A receptor ligands ( S )- N -{[1-(2-phenylethyl)pyrrolidin-2-yl]methyl}-3-[ 11 C]methylthiobenzamide ([ 11 C]( S )-PPMMB) (Ki = 4.3 nM) and the less active [ 11 C]( R )-PPMMB (Ki = 160 nM) by reduction of the disulfide dimer and subsequent [ 11 C]methylation of demethyl ( S )- and ( R )-PPMMB, respectively. Both radioligands showed similar brain distribution in mice with relatively higher affinity for the hippocampus being rich in 5-HT 1A receptors than for other brain regions. Uptake of [ 11 C]( S )-PPMMB was not reduced by carrier-loading nor by pretreatment with 5-HT 1A receptor ligands. [ 11 C]( S )-PPMMB is therefore not a suitable radioligand for mapping 5-HT 1A receptors using positron emission tomography.

N-[1-(2-phenylethyl)pyrrolidin-3-yl]-1-adamantanecarboxamides as novel 5-HT2 receptor antagonists

A series of 1-adamantanecarboxamides was synthesized and examined for their potency as a selective 5-HT2 receptor antagonist. We found (S)-N-[1-[2-(4-fluorophenyl)ethyl]pyrrolidin-3-yl]-1-adamantane carboxamide hydrochloride hydrate (10-(S), Y-39241) to have a high affinity and selectivity for 5-HT2 receptors, and this potent anti-platelet effect of Y-39241 was confirmed both in vitro and in vivo.

N-{[1-(2-phenylethyl)pyrrolidin-2-yl]methyl}cyclohexane-carboxamides as selective 5-HT1A receptor agonists

A series of benzamides was synthesized as selective agonists for the 5-HT1A receptor. It was found that (S)-N-[[1-(2-phenylethyl)pyrrolidin-2-yl]methyl]cyclohexanecarb oxamide(7-(S)) has potent and selective agonistic activity for the 5-HT1A receptor (5-HT1A; Ki 0.49 nmol/L, D2; IC50 = >1000 nmol/L, 5-HT2; Ki = 240 nmol/L).