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Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia

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Abstract

The so-called counterbalancing dopaminergic-cholinergic system has been studied in a clinical pharmacological investigation of neuroleptic-induced tardive dyskinesia. Eight hospitalized patients between the ages of 20 and 69 years were treated with α-methyl-para-tyrosine (AMPT), l-Dopa, physostigmine, scopolamine and biperiden. The results were evaluated blind with the help of video-technique. AMPT (3 g daily for 3 days) significantly reduced, while l-Dopa (1200 mg daily together with a peripheral decarboxylase inhibitor for 14 days) and biperiden (18 mg daily for 14 days) significantly precipitated/aggravated the dyskinesia. The effects of physostigmine and scopolamine have varied, which is discussed in relation to the existence of both hypo- and hypercholinergic stereotype.

It is concluded that dopaminergic hypersensitivity, cholinergic hypofunction and a reduced biological buffer capacity comprise important elements in the pathophysiology of tardive dyskinesia. Simple prophylactic and therapeutic directions are given based upon this conclusion.

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Authors and Affiliations

  1. Department E, Stc. Hans Hospital, 4000, Roskilde, Denmark

    J. Gerlach, N. Reisby & A. Randrup

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  1. J. Gerlach
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  2. N. Reisby
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  3. A. Randrup
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Gerlach, J., Reisby, N. & Randrup, A. Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia 34, 21–35 (1974). https://doi.org/10.1007/BF00421217

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