, Volume 34, Issue 1, pp 21–35 | Cite as

Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia

  • J. Gerlach
  • N. Reisby
  • A. Randrup
Human Pharmacology


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.

Key words

Tardive Dyskinesia Dopaminergic Hypersensitivity Cholinergic Hypofunctiom AMPT l-Dopa Physostigmine Scopolamine Biperiden 


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Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • J. Gerlach
    • 1
  • N. Reisby
    • 1
  • A. Randrup
    • 1
  1. 1.Department EStc. Hans HospitalRoskildeDenmark

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