A comprehensive review on the role of dopamine in the pathophysiology of tardive dyskinesia


  • Krishnaveni Kandasamy Department of Pharmacy Practice, Vivekanandha Pharmacy College for Women, Sankari, Salem, Tamil Nadu, India
  • Abinaya Paramanandham Department of Pharmacy Practice, JKKN College of Pharmacy, Kumarapalayam, Namakkal, Tamil Nadu, India
  • Goshika Russel Suthi Kumari Department of Pharmacy Practice, JKKN College of Pharmacy, Kumarapalayam, Namakkal, Tamil Nadu, India
  • Kameswaran Ramalingam Department of Pharmacy Practice, Pushpagiri College of Pharmacy, Thiruvalla, Kerala, India




Tardive dyskinesia, Drug-induced movement disorder, Involuntary movements, Dopamine receptor, Atypical anti psychiatric drugs


Tardive dyskinesia (TD) is a neurological syndrome characterized by involuntary, repetitive, and unusual movements that primarily impact the orofacial region while also extending to other body parts, encompassing chorea, dystonia, tics, buccolingual stereotypy, and akathisia. This condition stems from iatrogenic factors, particularly the chronic administration of medications that obstruct dopamine receptors. Predominantly implicated are antipsychotic drugs, utilized primarily for schizophrenia and bipolar disorder treatment. These drugs modulate dopamine levels, yet prolonged usage can induce alterations in dopamine receptor sensitivity and disruptions in dopaminergic pathways, consequently fostering TD. Dopamine, a pivotal neurotransmitter governing motor control, motivation, reward processing, and emotional regulation, exerts its effects through distinct dopamine receptor types, of which the D2 subtype assumes particular significance in TD development. The persistent blockade of D2 receptors by antipsychotics prompts a compensatory surge in receptor numbers and sensitivity, ultimately contributing to TD's emergence. In essence, TD reflects a complex interplay between medical intervention and neurological intricacies. The protracted influence of antipsychotics on dopamine receptors highlights the delicate equilibrium essential for optimal brain function. The unconventional movements characterizing TD underscore the intricate role of dopamine and its receptors in orchestrating neural equilibrium.


Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor and other hyperkinetic movement (N Y). 2013;3.

Stroup TS, Gray N. Management of common adverse effects of antipsychotic medications. World Psychiatry. 2018;17(3):341-56.

Caroff SN. Recent Advances in the Pharmacology of Tardive Dyskinesia. Clin Psychopharmacol Neurosci. 2020;18(4):493-506.

Stegmayer K, Walther S, van Harten P. Tardive Dyskinesia Associated with Atypical Antipsychotics: Prevalence, Mechanisms and Management Strategies. CNS Drugs. 2018;32(2):135-47.

Cornett EM, Novitch M, Kaye AD, Kata V, Kaye AM. Medication-Induced Tardive Dyskinesia: A Review and Update. Ochsner J. 2017;17(2):162-74.

Vasan S, Padhy RK. Tardive Dyskinesia. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2023.

Mishra A, Singh S, Shukla S. Physiological and Functional Basis of Dopamine Receptors and Their Role in Neurogenesis: Possible Implication for Parkinson's disease. J Exp Neurosci. 2018;12:1179069518779829.

Ford CP. The role of D2-autoreceptors in regulating dopamine neuron activity and transmission. Neuroscience. 2014;282:13-22.

Lee HJ, Weitz AJ, Bernal-Casas D, Duffy BA, Choy M, Kravitz AV, et al. Activation of Direct and Indirect Pathway Medium Spiny Neurons Drives Distinct Brain-wide Responses. Neuron. 2016;91(2):412-24.

Laprade N, Radja F, Reader TA, Soghomonian JJ. Dopamine receptor agonists regulate levels of the serotonin 5-HT2A receptor and its mRNA in a subpopulation of rat striatal neurons. J Neurosci. 1996;16(11):3727-36.

Farah A. Atypicality of atypical antipsychotics. Primary Care Companion to The Journal of Clinical Psychiatry. 2005;7(6):268-74.

Czoty PW, Gage HD, Nader MA. Differences in D2 dopamine receptor availability and reaction to novelty in socially housed male monkeys during abstinence from cocaine. Psychopharmacology (Berl). 2010;208(4):585-92.

Yin J, Barr AM, Ramos-Miguel A, Procyshyn RM. Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review. Curr Neuropharmacol. 2017;15(1):174-83.

Brisch R, Saniotis A, Wolf R, Bielau H, Bernstein HG, Steiner J, et al. The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue. Front Psychiatry. 2014;5:47.

Hernandez G, Mahmoudi S, Cyr M, Diaz J, Blanchet PJ, Lévesque D. Tardive dyskinesia is associated with altered putamen Akt/GSK-3β signaling in nonhuman primates. Movement Disorder. 2019;34(5):717-26.

Benoit-Marand M, Borrelli E, Gonon F. Inhibition of dopamine release via presynaptic D2 receptors: time course and functional characteristics in vivo. J Neurosci. 2001;21(23):9134-41.

Seigneurie AS, Sauvanaud F, Limosin F. Dyskinésies tardives induites par les antipsychotiques : données actuelles sur leur prévention et prise en charge [Prevention and treatment of tardive dyskinesia caused by antipsychotic drugs]. Encephale. 2016;42(3):248-54.

Seeman P. All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2(high) receptors. CNS Neuroscience & Therapeutics. 2011;17(2):118-32.

Malik P, Andersen MB, Peacock L. The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia. Pharmacology Biochemistry and Behavior. 2004;78(4):805-10.

Mahmoudi S, Lévesque D, Blanchet PJ. Upregulation of dopamine D3, not D2, receptors correlates with tardive dyskinesia in a primate model. Movement Disorders. 2014;29(9):1125-33.

Ślifirski G, Król M, Turło J. 5-HT Receptors and the Development of New Antidepressants. Int J Mol Sci. 2021;22(16):9015.

Oda Y, Kanahara N, Iyo M. Alterations of Dopamine D2 Receptors and Related Receptor-Interacting Proteins in Schizophrenia: The Pivotal Position of Dopamine Supersensitivity Psychosis in Treatment-Resistant Schizophrenia. Int J Mol Sci. 2015;16(12):30144-63.

Goldstein DS. The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Do Not Know. Int J Mol Sci. 2021;22(11):5999.

Song J, Kim J. Degeneration of Dopaminergic Neurons Due to Metabolic Alterations and Parkinson's Disease. Front Aging Neurosci. 2016;8:65.

Seeman P. Atypical antipsychotics: mechanism of action. Canad J Psychiatry. 2002;47(1):27-38.

Tammenmaa-Aho I, Asher R, Soares-Weiser K, Bergman H. Cholinergic medication for antipsychotic-induced tardive dyskinesia. Cochrane Database Systemat Rev. 2018;3(3):CD000207.

Stahl SM. Mechanism of action of vesicular monoamine transporter 2 (VMAT2) inhibitors in tardive dyskinesia: reducing dopamine leads to less "go" and more "stop" from the motor striatum for robust therapeutic effects. CNS Spectrums. 2018;23(1):1-6.

Govoni S, Racchi M, Masoero E, Zamboni M, Ferini-Strambi L. Extrapyramidal symptoms and antidepressant drugs: neuropharmacological aspects of a frequent interaction in the elderly. Mol Psychiatry. 2001;6(2):134-42.

Shireen E. Experimental treatment of antipsychotic-induced movement disorders. J Exp Pharmacol. 2016;8:1-10.




How to Cite

Kandasamy, K., Paramanandham, A., Suthi Kumari, G. R., & Ramalingam, K. (2023). A comprehensive review on the role of dopamine in the pathophysiology of tardive dyskinesia. International Journal of Research in Medical Sciences, 11(10), 3925–3930. https://doi.org/10.18203/2320-6012.ijrms20233065



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