Referenced in: none

Automatically associated channels: Kir2.1 , Kir3.1

Title: LB50053: a 5-hydroxytrypamine(1a) agent with a high binding affinity and a potency evoking a K(+) current.

Authors: Han-Seop Kim, Taesup Cho, Changho Lee, Hyun Joo, Seung Kim, Churl K Min

Journal, date & volume: Pharmacology, 2002 Aug , 65, 175-81

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12174831

Abstract
The newly synthesized N-substituted derivative of 3-aryl-pyrrolidine LB50053, 2-[4-[3-(4-fluoro)-phenylpyrrolidine-1-yl] - butyl]-1,2- benzisothiazol -3(2H)-one-1,1-dioxide, was studied in receptor-binding assays and in electrophysiological measurements. Competitive binding experiments with various radioligands to the rat fore-brain revealed that the (S)-enantiomer of LB50053 had a high affinity (Ki 4.2 nmol/l) and a high selectivity for 5-HT(1A) receptors as compared with 5-HT(2A), D(1) dopamine, D(2) dopamine, or (alpha(2)-adrenergic receptor. In Xenopus oocytes, where coupling of the 5-HT(1A) receptor to the G protein activated inwardly rectifying K(+) channel 1(GIRK1) was established, (S)-LB50053 evoked an inward K(+) current through GIRK1 in a manner consistent with a partial agonism. The K(d) value deduced from the dose-response relationships of the 5-HT(1A) receptor full agonist 8-OH-2-(di-n-propylamino)-1,2,3,4-tetrahydronaphthalene and (S)-LB50053 according to Waud analysis was 64.60 nmol/l. These results demonstrate that LB50053 is a 5-HT(1A) receptor partial agonist and thus can be used asa therapeutic or pharmacological research tool for 5-HT(1A) receptor mediated events in the future.