Therapeutic role of 5-HT1A receptors in the treatment of schizophrenia and Parkinson's disease

Abstract

5-HT(1A) receptors have long been implicated in the pathogenesis and treatment of anxiety and depressive disorders. Recently, several lines of studies have revealed new insights into the therapeutic role of 5-HT(1A) receptors in treating schizophrenia and Parkinson's disease. Specifically, 5-HT(1A) receptors seem to be a promising target for alleviating antipsychotic-induced extrapyramidal side effects (EPS) and cognitive/affective disorders in schizophrenia. In the treatment of patients with Parkinson's disease, 5-HT(1A) agonists are expected to improve not only affective symptoms (e.g., anxiety and depression), but also the core parkinsonian symptoms as well as antiparkinsonian agents-induced side effects (e.g., L-DOPA-induced dyskinesia). Here, the therapeutic mechanisms mediated by 5-HT(1A) receptors in schizophrenia and Parkinson's disease are reviewed. This evidence should encourage discovery of new 5-HT(1A) ligands, which can resolve the unmet clinical needs in the current therapy.

Figure 1

Signal transduction pathways of 5‐HT_1A receptor (A) and the mechanism underlying anxiolytic and antidepressant actions of 5‐HT_1A agonists (B). GIRK, G‐protein‐gated inwardly rectifying potassium channel; PK A, protein kinase A.

Figure 2

Current therapeutics, unmet clinical needs and therapeutic role of 5‐HT_1A receptors in the treatment of schizophrenia.

Figure 3

Therapeutic mechanisms and action sites of 5‐HT_1A agonists and 5‐HT_2A antagonists in ameliorating the extrapyramidal motor disorders. DA, dopamine; Glu, glutamate; (+), excitation; (−), inhibition.

Figure 4

Current therapeutics, unmet clinical needs and therapeutic role of 5‐HT_1A receptors in the treatment of Parkinson's disease. AADCI, aromatic L‐amino acid decarboxylase inhibitors; ACh, acetylcholine; MAO‐B, monoamine oxidase‐B; COMT, catechol‐O‐methyltransferase.