Characterization of RO4583298 as a novel potent, dual antagonist with in vivo activity at tachykinin NK₁ and NK₃ receptors.

ABSTRACT:

Background and purpose

Clinical results of osanetant and talnetant (selective-NK₃ antagonists) indicate that blocking the NK₃ receptor could be beneficial for the treatment of schizophrenia. The objective of this study was to characterize the in vitro and in vivo properties of a novel dual NK₁/NK₃ antagonist, RO4583298 (2-phenyl-N-(pyridin-3-yl)-N-methylisobutyramide derivative).

Experimental approach

RO4583298 in vitro pharmacology was investigated using radioligand binding ([³H]-SP, [³H]-osanetant, [³H]-senktide), [³H]-inositol-phosphate accumulation Schild analysis (SP- or [MePhe⁷]-NKB-induced) and electrophysiological studies in guinea-pig substantia nigra pars compacta (SNpc). The in vivo activity of RO4583298 was assessed using reversal of GR73632-induced foot tapping

SUBMITTER: Malherbe P 

PROVIDER: S-EPMC3042203 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature