Pharmacodynamics Actions RO5073012 has high
affinity for the mouse, rat,
cynomolgus monkey, and human TAAR1 (Ki = 0.5–6nM), is highly
potent and selective as an agonist of the TAAR1 of these species ( = 8.8–25nM), and has relatively low
intrinsic activity at the TAAR1 of these species ( = 24–43% relative to
β-phenethylamine). Conversely however, and in contrast to other TAAR1 partial agonists, RO5073012 non-significantly reduced the locomotor activity induced by
amphetamine in normal mice. The reasons for this difference from other TAAR1 partial agonists are unclear, though RO5073012 has notably lower TAAR1 efficacy than other TAAR1 partial agonists. RO5073012 reduces basal locomotor activity in
transgenic mice with TAAR1
overexpression.
Amphetamine produces only weak
locomotor stimulation in mice with TAAR1 overexpression, and RO5073012, by
antagonizing the TAAR1, has been found to restore
dextroamphetamine-induced hyperlocomotion in this context.
Pharmacokinetics The drug has favorable
physicochemical and
pharmacokinetic properties for use
in vivo. ==History==