Table 1.
Main pharmacological properties of lurasidone
| Primary pharmacology |
| In vitro studies |
| High affinity for human D2L, serotonin 5-HT2A, 5HT1A and 5HT7 receptors.a |
| Partial agonism at human 5HT1A and antagonism at human D2L and 5-HT7 receptors.a |
| High affinity for human α2c-adrenoceptorsa, and relatively high affinity for α1, α2, α2A adrenoreceptor types. |
| Little binding affinity for 5-HT3, 5-HT4, noradrenaline β, β1, β2, adenosine A1, A2, benzodiazepine, cholecystokinin CCKA, CCKB, |
| L-type Ca2+ channel, N-type Ca2+ channel, GABAA, glutamate AMPA, kainate, NMDA, glycine, histamine H1, muscarin M1, M2, nicotine, opiate, sigma, 5-HT uptake sites, and dopamine uptake sites. |
| Antipsychotic-like activity |
| Inhibition of methamphetamine-induced hyperactivity in rats,a apomorphine-induced stereotyped behavior in rats, apomorphine-induced climbing behavior in mice and conditioned avoidance response in rats. |
| Antagonism of central 5-HT2 receptors, as shown by dose-dependent inhibition of tryptamine-induced clonic forepaw seizurea,b and p-chloroamphetamine-induced hyperthermia in mice and rats. |
| Mood-stabilizing effects |
| Inhibition of conditioned fear stress-induced freezing behavior in rats. |
| Increased punished drinking response (number of shocks received) in Vogel’s water lick conflict test. |
| Increased social interaction time spent by pairs of naive rats under brightly illuminated conditions in the social interaction test. |
| Cognitive effects |
| Improvement of learning and of memory impairment induced by the NMDA-receptor antagonist MK-801 and memory impairment induced by the muscarinic receptor antagonist scopolamine in rats. |
| Effects on monoamine metabolism |
| Enhancement of the contents of dopamine metabolites DOPAC and HVA and boosted dopamine turnover in the frontal cortex and striatum, like other antipsychotic agents. |
| Secondary pharmacology |
| Potential extrapyramidal symptom liability |
| No cataleptogenic activity in either mice or rats, whereas comparator antipsychotics dose-dependently induced catalepsy. |
| No significant effects on the pole-descending time and forepaw reaction time in animal models, unlike comparator antipsychotics. |
| Potential for CNS depression |
| Weaker effects than comparator antipsychotics on spontaneous locomotor activity, hexobarbital-induced anesthesia, muscle relaxation and motor coordination and MES-induced seizures in animal models. |
Notes:
a
These properties are shared by metabolites ID-14283 and ID-14326, and
b
metabolite ID-11614 or 1-(1,2-benzisothiazol-3-yl)-piperazine.