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Targeting Dopaminergic Pathways: Current and Emerging Dopamine Inhibitors in Neurological and Psychiatric Disorders

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CNS Neurol Disord Drug Targets. 2026 Mar 10. doi: 10.2174/0118715273431536251202114957. Online ahead of print.

ABSTRACT

Dopaminergic signaling plays a central role in regulating motor control, reward processing, and emotional balance. Dysregulation of dopamine pathways is implicated in multiple neuropsychiatric disorders. This review primarily focuses on current and emerging dopaminergic inhibitors, including dopamine receptor antagonists, dopamine transporter blockers, and indirect modulators, while also comparatively addressing pro-dopaminergic approaches. Emphasis is placed on their mechanisms, clinical applications, adverse effects, and future therapeutic directions in neurological and psychiatric disorders. We conducted a comprehensive review of preclinical and clinical studies on dopamine receptor antagonists, dopamine transporter blockers, indirect modulators, and novel dopaminergic drug-delivery approaches. Typical and atypical antipsychotics are essential in the treatment of schizophrenia, dopamine transporter inhibitors such as methylphenidate are firstline in ADHD, and monoamine oxidase inhibitors play a key role in Parkinson’s disease. In addition, dopaminergic modulation provides adjunctive benefits through agents like bupropion. However, long-term use can result in extrapyramidal symptoms and metabolic disturbances. Recent advances include subtype-selective receptor modulators, nanotechnology-driven delivery systems, and combination therapies targeting complementary neurotransmitter systems. Although dopaminergic agents offer therapeutic benefits, limitations such as side effects and poor receptor selectivity persist. Emerging strategies, including targeted delivery and personalized treatment approaches, hold promise for improving efficacy and tolerability in dopaminergic therapy.

PMID:41833047 | DOI:10.2174/0118715273431536251202114957

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