Signal transduction and functional selectivity of F15599, a preferential post-synaptic 5-HT1A receptor agonist.

ABSTRACT:

Background and purpose

Activation of post-synaptic 5-HT(1A) receptors may provide enhanced therapy against depression. We describe the signal transduction profile of F15599, a novel 5-HT(1A) receptor agonist.

Experimental approach

F15599 was compared with a chemical congener, F13714, and with (+)8-OH-DPAT in models of signal transduction in vitro and ex vivo.

Key results

F15599 was highly selective for 5-HT(1A) receptors in binding experiments and in [(35)S]-GTPgammaS autoradiography of rat brain, where F15599 increased labelling in regions expressing 5-HT(1A) receptors. In cell lines expressing h5-HT(1A) receptors, F15599 more potently stimulated extracellular signal-regulated kinase (ERK1/2) phosphorylation, compared with G-protein activation, internalization of h5-

SUBMITTER: Newman-Tancredi A 

PROVIDER: S-EPMC2697830 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature