Tardive dyskinesia dopaminergic receptor

Because of the rather nonspecific blockade of dopaminergic receptors, antipsychotics are associated with several adverse side effects. The most serious of these are abnormal movement patterns that resemble tardive dyskinesia, Parkinson disease, and other lesions associated with the extrapyramidal system. In some cases, these aberrant motor activi-... 

Qll Other neuroleptic agents include phenothiazines, such as chlorpromazine, promazin and thioridazine, and thioxanthines, such as flupenthixol. The non-specific blockade of dopaminergic receptors afforded by these drugs leads to development of side effects, such as endocrine dysfunction and extrapyramidal motor symptoms. The unwanted antagonism of motor tracts results in extrapyramidal side effects, such as Parkinsonism and tardive dyskinesia. The latter is associated with involuntary movements of the face, limbs and trunk. Chronic neuroleptic therapy can inhibit the release of GABA. This in turn leads to changes in mobility. 

Muscarinic receptor blockers may improve muscle rigidity and tremor in Parkinsons disease but result in very little improvement in bradykinesia thus, they are mainly considered as adjunctive to the use of drugs that improve dopaminergic function. Selegiline is the inhibitor of MAO type B, and pramipexole is a non-ergot DA receptor agonist. Carbidopa inhibits peripheral AAAD (dopa decarboxylase) tolcapone is an inhibitor of COMT. Levodopa causes a high incidence of dose-dependent dyskinesias that are not slow in onset, like tardive dyskinesia that results from chronic administration of DA receptor blockers. 

Contrary to the usual activity of antipsychotics, clozapine exhibits regional specific anti-dopaminergic profile having, relatively mild antagonism on the extrapyramidal dopaminergic action and this could be responsible for its low propensity to produce extrapyramidal side effects e.g., dystonias, tardive dyskinesia. It also causes greater blockade of dopamine D-1 receptors and however, it is not yet established whether such action precisely contributes to its antipsychotic therapeutic activity. 

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