Phenothiazine-Related Critical Conditions: a Mini-Review

Objective. The aim of this review is to summarize the pathological mechanisms associated with the toxicity of phenothiazines in overdose. Materials and methods. A database search was conducted on PubMed, Google Scholar and eLibrary were used to identify original research articles, clinical reports, review articles, editorials, commentaries, and brief communications. Additional sources not identified through the search of these databases were analyzed after reviewing the reference lists of the selected articles. Articles were selected based on the relevance of the title and abstract to the purpose of this review. Results. This review analyzes the mechanisms of action of phenothiazines in the context of their long-term clinical use and in overdose, as well as the mechanisms of action of proposed potential areas of application of phenothiazines. Clinical manifestations of phenothiazine poisoning are predominantly characterized by antagonism of dopamine D₁–D₄ receptors, histamine H₁ receptors, α₁–α₂ α-adrenergic receptors and muscarinic acetylcholine receptors M₁–M₂. In addition, phenothiazines are able to increase the permeability of the blood-brain barrier through apoptosis, increase global methylation, effectively enhance chemotherapy of some tumors and provide neuroprotection by reducing GFAP production (PKC-δ/NOX/MnSOD pathway). Conclusions. Given the potential for new applications of phenothiazines, further study of the effects of phenothiazines on the central nervous system in overdose, with a focus on repeat overdose episodes, is important at the morphological level to identify the underlying morphological substrate. Further study of the mechanisms associated with phenothiazine use is needed to develop more effective therapeutic strategies to improve patient outcome, not only in psychiatry but also in other disciplines.