ST2472 was shown to bind to multiple receptors, thus resembling the affinity spectrum of atypical antipsychotics. The present study investigates its in-vivo potential antipsychotic effects. ST2472 is effective in the conditioned avoidance response (CAR) test in rats (ED50=1.5 mg/kg p.o.), a model sensitive to antipsychotics. It antagonizes amphetamine-induced hypermotility at dosages (minimal effective dose=0.7 mg/kg p.o.) that are lower than those necessary to antagonize amphetamine-induced stereotypy (minimal effective dose=30 mg/kg p.o.), in rats. This finding, together with the fact that ST2472 does not induce catalepsy in rodents at up to 100 mg/kg p.o., indicates that ST2472 has very low liability to induce extrapyramidal side-effects. ST2472 does not increase prolactinaemia after chronic treatment. In mice, ST2472 does not appear to alter blood pressure and heart rate in a significant fashion. In conclusion, ST2472 seems to be an antipsychotic with lower liability to produce side-effects than other antipsychotics, such as haloperidol, risperidone, olanzapine and clozapine, which were evaluated as reference drugs.

We compared the potency of the interaction of three antipsychotic drugs, i.e. chlorpromazine (CPZ), haloperidol (Hal) and sulpiride (Sul), with the plasma membrane in the rat brain. CPZ loading (⩾100 μm) dose-dependently increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-d-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On the other hand, a higher concentration of Hal (1 mm) was required to observe these effects. However, Sul failed to change membrane permeability and fluidity even at a high concentration (1 mm). These results indicated the following ranking of the potency to interact with the membrane: CPZ>Hal>Sul. The difference among antipsychotic drugs in the potency to interact with the plasma membrane as revealed in the present study may be partly responsible for the difference among the drugs in the probability of inducing extrapyramidal side-effects such as parkinsonism and tardive dyskinesia.