Background and purpose
Clinical
Purpose
Clinical
Results
RO4583298 has a high-affinity for NK&sub1; (human and gerbil) and NK&sub3; (human, cynomolgus monkey, gerbil and guinea-pig) receptors and behaves as a pseudo-irreversible antagonist. Unusually it binds with high-affinity to mouse and rat NK&sub3;, yet with a partial non-competitive mode of antagonism. In guinea-pig SNpc, RO4583298 inhibited the senktide-induced potentiation of spontaneous activity of dopaminergic neurones with an apparent non-competitive mechanism of action. RO4583298 (p.o.) robustly blocked the GFT response, and inhibited the MTW. Conclusions and implications: RO4583298 is a high-affinity, non-competitive, long-acting in vivo NK&sub1;/NK&sub3; antagonist; hence providing a useful in vitro and in vivo pharmacological tool to investigate the roles of NK&sub1; and NK&sub3; receptors in psychiatric disorders.