New Atypical Antipsychotics in the Treatment of Schizophrenia and Depression.

Schizophrenia and depression are heterogeneous disorders. The complex pathomechanism of the diseases imply that medication responses vary across patients. Many psychotropic drugs are available but achieving optimal therapeutic effect can be challenging. The evidence correlates well with clinical observations, suggesting that new atypical antipsychotic drugs are effective against negative and cognitive symptoms of schizophrenia, as well as against affective symptoms observed in depression. The purpose of this review presents the background and evidence for the use of the new second/third-generation antipsychotics (aripiprazole, cariprazine, lurasidone, asenapine, brexpiprazole, lumateperone, pimavanserin) in treatment of schizophrenia and depression. We have first provided a brief overview of the major neurobiological underpinnings of schizophrenia and depression. We then shortly discuss efficacy, safety and limitations of ongoing pharmacotherapy used in depression and schizophrenia. Mainly, we have focused this review on the therapeutic potential of new atypical antipsychotic drugs-currently existing-to be effective in psychotic, as well as in affective disorders.

p-Nitrophenoxycarbonyl derivatives of Boc-protected diaminoalkanes in the synthesis of enkephalin peptidomimetics.

The synthesis of p-nitrophenoxycarbonyl derivatives of 1-Boc-1,2-diaminoethane, 1-Boc-1,3-diaminopropane and 1-Boc-1,4-diaminobutane is described. These derivatives were used to synthesize five peptidomimetics, analogues of enkephalin, containing alkylurea units inside the peptide chain and at the C-terminal. All syntheses were carried out in solid phase on MBHA resin. Peptidomimetics with alkylurea units inserted into the peptide chain were synthesized using the standard method employing the Boc-strategy, with TFA deprotection and HF cleavage. The analogue containing a C-terminal alkylurea unit was synthesized using the Boc-strategy, with HCl/dioxane deprotection and TFA cleavage. All of the analogues were examined for opioid activity in GPI and MVD assays. The activity of the analogue containing a C-terminal alkylurea unit was comparable to that of [Leu5]-enkephalin, while the other analogues were less active.