Reference

Synthesis and binding properties of the fluorinated substituted benzamide [3H]NCQ 115, a new selective dopamine D2 receptor ligand

Synthesis and binding properties of the fluorinated substituted benzamide [3H]NCQ 115, a new selective dopamine D2 receptor ligand. Hall, Haakan; Hoegberg, Thomas; Halldin, Christer; Bengtsson, Stefan; Wedel, Ilse (Astra Res. Cent. AB, Soedertoelje S-15185, Swed.). Eur. J. Pharmacol., 201(1), 1-10 (English) 1991. CODEN: EJPHAZ. ISSN: 0014-2999. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 8 [3H]NCQ 115 (I) was prepd. by acylation of (R)-(2-aminomethyl)-1-([2,5-3H]-4-fluorobenzyl)pyrrolidine, which was obtained in a stereoconservative synthesis from (R)-prolinamide. Purifn. by reversed phase HPLC gave I with a radiochem. purity of >99% and a specific activity of 0.97 GBq/mmol (36 Ci/mmol). Satn. analyses, assocn. and dissocn. kinetics as well as binding competition with several compds. of various classes were performed with I in rat striatal homogenates. Satn. analyses in vitro showed that I bound to a single binding site with a Kd = 214 pM and Bmax = 35.4 fmol/mg. The binding of I was dependent upon Na, since the no. of binding sites was altered when Na were excluded from the incubation medium. I inhibited the binding of [3H]raclopride to dopamine D2 receptors with high affinity (Ki = 147 pM), having much lower affinity for other receptors. The affinity of this substituted 1-benzyl-2-pyrrolidinylmethylbenzamide was confined to the (R)-enantiomer, which contrasts with that of the corresponding N-Et derivs. such as FLB 457, raclopride, eticlopride, sulpiride and NCQ 298, where the pharmacol. activity is found in the (S)-enantiomer. Thus, I binds to dopamine D2 receptors in the rat striatum with high affinity and high selectivity. I can also be used for in vivo binding studies of the brain. 107188-75-0 and 62937-45-5 are just another two chemicals used in this study. 18F-labeled I may be a suitable ligand for positron emission tomog. studies of the human brain in vivo. .