Schizophrenia

At the molecular level, there is the constant process of antipsychotic binding to D2, followed by antipsychotic dissociation and re-binding to D2.

"Typical" or traditional antipsychotics such as haloperidol and chlorpromazine disassociate very slowly from the D2 receptor, which contributes to Parkinsonism by reducing the access of dopamine molecules to the receptor.

"Atypical" antipsychotics, such as quetiapine, clozapine, remoxipride, paliperidone (9-hydroxy-risperidone), amoxapine, perlapine and aripiprazole, bind loosely and rapidly dissociate from D2 before re-binding. This "fast-off-D2 principle" provides microseconds of time to permit dopamine molecules access to D2 and this access, in turn, minimizes extrapyramidal (movement disorders) and related side-effects.

Clera has developed a number of novel small-molecule drug candidates that have optimized "fast-off" affinity for D2 receptors and low affinity for other receptors, thereby reducing the risk of extrapyramidal signs, dizziness and cardiac effects. Based on receptor profiling, they are predicted to have strong antipsychotic activity and a low or no risk of Parkinsonism, hyperprolactinemia, tardive dyskinesia, obesity, diabetes or abnormal ECG.

Depression

Our CLR3001 Phase II compound has a unique antidepressant mechanism of action.