Use of a cloned G-protein-coupled receptor in the in vitro screening of psychotropic compounds

By Konings, P.N.M. - Vanderheyden, P.M.L. - Stam, N.J. - Delft, A.M.L. van. - Ruigt, G.S.F.

In the initial preclinical phase of the development of new psychotropic agents, potential drugs are generally characterised by in vitro receptor binding studies using rat brain preparations. We have recently, at this stage, incorporated assays using cell lines transfected with cloned receptors (1). One of the important 5-hydroxytryptamine (5-HT) receptor subtypes used for screening of these compounds is the 5-HT(1A) receptor, characterised by binding of the selective agonist [3H]-8-OH-DPAT. Results from these binding studies in rat hippocampus membranes appear to correlate very well with results obtained from membranes of fibroblasts expressing cloned human 5-HT(1A) receptors. This indicates that cloned receptors can be used to characterise psychotropic agents, thereby significantly reducing the number of experimental animals required. Moreover, the information obtained is likely to be of greater relevance for the evaluation of the potential therapeutic action of a drug in man.