Tardive dyskinesia from antipsychotic

Tardive dyskinesia from antipsychotic agents (dopamine D2 and D3 receptor variants)... 

Chlorpromazine, the first modern drug to be used in the treatment of schizophrenia and other psychotic disorders, was introduced into psychiatry in 1952 [61]. It was followed by a number of other drugs for the treatment of these conditions (e.g., haloperidol, thioridazine). These were also called neuroleptics because of their neurological side effects, such as parkinsonian syndrome and tardive dyskinesia. Tardive dyskinesia is a movement disorder characterized by involuntary movements of the face and limbs. The antipsychotic properties of these drugs were inseparable from the extrapyramidal effects. 

CYP2D6 /3 blockers, antidepressants, antipsychotics, codeine, debrisoquine, dextromethorphan, encainide, flecainide, fluoxetine, guanoxan, N-propylajmaline, perhexUine, phenacetin, phenformin, propafenone, sparteine Tardive dyskinesia from antipsychotics, narcotic side effects, codeine efficacy, imipramine dose requirement, /3 blocker effect... 

By contrast, studies of the dopamine D -like receptors have found evidence for the association of the receptor with disease (66) these studies have been replicated (41,42). From among the multitude of these studies, only selected examples are reviewed here. For example, evidence both for and against the association of the dopamine D -like receptors with schizophrenia has been reported. Polymorphisms of the dopamine receptor, including the third intracellular loop VNTR, alter dopamine receptor expression. In addition to association with schizophrenia (3,67-70), the dopamine polymorphisms have been associated with the genetic basis of the variable efficacy of antipsychotics such as clozapine (or neuromuscular toxicity—tardive dyskinesia) (69,71,72). Similarly, promoter SNPs have been associated with altered clozapine efficacy (67,68,73). 

Various neuroleptics are also used for nonpsychiatric purposes, usually in smaller doses for shorter durations. However, severe effects can sometimes develop from these limited uses. Reserpine (Serpasil) is a neuroleptic that is more often used to suppress the symptoms of tardive dyskinesia (chapter 4). Prochlorperazine (Compazine) is used as an antiemetic and rarely as a neuroleptic. If given in sufficient doses to manifest psychoactive effects, these drugs produce the same emotional indifference as the other antipsychotic drugs. 

Four patients developed tardive dyskinesia while taking conventional antipsychotic drugs and were switched to sertindole (5). Three apparently recovered from the movement disorder. In the other patient sertindole monotherapy was not sufficient to reduce the movement effects, but combination treatment with tetrabe-nazine resulted in a greater reduction in extrapyramidal symptoms. There was no evidence of QTC prolongation in these patients, but one patient gained 8 kg in weight. 

There is some evidence from a study in animals that chronic administration of drugs such as chlorpromazine (an antipsychotic) results in increased levels of manganese in the brain, including the caudate nucleus (Weiner et al. 1977). Chronic chlorpromazine treatment sometimes results in tardive dyskinesia, and manganese deposition in the brain might contribute to this condition. It has not been determined whether excess manganese exposure increases the risk of chlorpromazine-induced dyskinesia. 

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