New groups of neuroleptic drugs – phosphodiesterase inhibitors 10A. Narrative review

Aim.
This work aims to provide a narrative review of the literature on a new group of neuroleptic drugs, which may potentially include phosphodiesterase 10A (PDE10A) inhibitors.

Literature review.
Inhibition of phosphodiesterase 10A activity increases the concentration of cyclic nucleotides in striatal dopaminergic neurons. The D2 receptors stimulated by dopamine inhibit adenylate cyclase activity, leading to a reduction in intracellular cAMP levels, decreased protein kinase A activity, and lower expression of proteins regulated by the transcription factor CREB. Blocking the D2 dopamine receptor with a neuroleptic increases intracellular cAMP levels, similarly to PDE10A inhibition. Unlike dopamine D2 receptor antagonists, PDE10A inhibitors do not cause extrapyramidal symptoms or induce metabolic syndrome. Several phosphodiesterase 10A inhibitors have already been synthesised and are currently undergoing phase II clinical trials.

Conclusions.
Phosphodiesterase 10A inhibitors represent a new class of neuroleptic drugs that do not cause adverse effects such as metabolic syndrome or parkinsonian symptoms.