An updated overview of alkaloids for the prevention and treatment of metabolic dysfunction-associated steatotic liver disease.

According to the World Health Organization, schizophrenia is a chronic disorder that affects around 1% of the global population []. To manage and alleviate its symptoms, various antipsychotic drugs have been developed, with the dopamine D receptor (D2R) being one of the primary pharmacological targets []. First-generation antipsychotics, such as haloperidol, were discovered around the same time as D2R identification and exhibit high selectivity for this receptor []. However, prolonged use of these drugs is associated with extrapyramidal symptoms (EPS), which manifest as movement disorders similar to those seen in Parkinson’s disease [,,,]. Second-generation antipsychotics, such as risperidone, have demonstrated a reduced incidence of EPS. Nevertheless, their use has been associated with an increased risk of metabolic side effects, including diabetes and hyperprolactinemia [,,,]. In this context, Jacques van Rossum [] proposed that all antipsychotics act as antagonists of the D2R, an exception to this model is aripiprazole, which under certain physiological conditions functions as a partial agonist []. Due to this unique pharmacological profile, aripiprazole is often classified as a third-generation antipsychotic [,]. D2R belongs to the class of G-protein-coupled receptors (GPCRs), a large family of transmembrane receptors that regulate intracellular signaling cascades associated with key physiological processes. The pharmacological relevance of GPCRs is substantial, as approximately 30% of the currently available drugs target these receptors [,,]. Structurally, GPCRs are characterized by a bundle of seven transmembrane -helices (TM1–TM7), an intracellular helix (H8), three extracellular loops (ECL1–ECL3), and three intracellular loops (ICL1–ICL3). The N-terminus (N-ter) is oriented toward the extracellular space, while the C-terminus (C-ter) resides intracellularly.