Vortioxetine's pharmacological profile in rodents is summarized
in Table 2. In general, the doses used in the preclinical pharmacology
studies were chosen to be equivalent to clinical doses based on the
level of SERT occupancy determined by ex vivo autoradiography
(Fig. 2 and discussed inmore detail in Section 2.2.1). In rats, vortioxetine
preferentially occupies the 5-HT3 receptor and the SERT at the lower
end of the dose spectrum (0.3–10 mg/kg, s.c.) whereas the other 5-HT
receptors are occupied at the higher end of the dose spectrum (Fig. 2).
Vortioxetine's lower affinity for 5-HT1A and 5-HT7 receptors in rats
compared to humans may mean that the net pharmacodynamic effects
of vortioxetine mediated through these receptors is underestimated in
the rat.