Comparative analysis between muscarinic and dopamine receptor in antipsychotic activity

Schizophrenia and related psychotic disorders are primarily treated with antipsychotic drugs targeting dopamine and muscarinic receptors. This review presents a comparative analysis of the antipsychotic activity of agents acting on these receptors, including KarXT (Xanomeline-trospium) olanzapine, clozapine, betel nut, Withania somnifera, haloperidol, chlorpromazine, Ginkgo biloba, and aporphine alkaloids. Dopamine receptor antagonists, such as haloperidol and chlorpromazine, have been the cornerstone of antipsychotic therapy but are associated with extrapyramidal side effects and tardive dyskinesia. Atypical antipsychotics like olanzapine and clozapine exhibit a mixed dopamine and muscarinic receptor profile, offering better symptom control but increasing the risk of metabolic and anticholinergic side effects. KarXT (Xanomeline-trospium) a novel muscarinic agonist-antagonist combination, represents a promising approach by bypassing dopamine-related adverse effects while maintaining efficacy. Traditional and plant-based compounds, such as betel nut, Withania somnifera, and Ginkgo biloba, modulate muscarinic and dopamine pathways and offer potential adjunctive benefits. Aporphine alkaloids, found in various plant species, exhibit dopamine receptor partial agonist activity and may hold promise for future drug development. This comparative review highlights the therapeutic advantages and limitations of muscarinic and dopamine receptor-targeting drugs, emphasizing the need for novel treatments that balance efficacy and safety in managing psychosis.