, Volume 75, Issue 1, pp 9–15 | Cite as

Acute extrapyramidal side effects: Serum levels of neuroleptics and anticholinergics

  • Larry Tune
  • Joseph T. Coyle
Original Investigations


An assay technique for measuring anticholinergic drugs in human serum based upon their inhibition of the specific binding of [3H]-quinuclidinyl benzilate to rat brain muscarinic receptors is described. The assay was validated by demonstrating a close correlation (r=0.99) between serum levels of nortriptyline measured by the radioenzymatic assay and a GLC technique. The assay measures free anticholinergics, and under standard assay conditions, approximately 95% of benztropine is bound to serum protein. Marked variation in serum anticholinergic levels in patients receiving the same oral dose was observed, and in individual patients there was a non-linear relationship between increasing oral dose and serum anticholinergic levels.

In a cross-sectional study of 109 patients receiving concurrently neuroleptics and antichlinergics, there was no correlation (r=0.029) between serum neuroleptic levels measured by a radioreceptor assay and extrapyramidal side effects (EPS). In the patients whose serum anticholinergic levels were also determined, there was a significant inverse correlation (r=0.44) between anticholinergic levels and EPS. In this cohort of patients, there was no significant correlation between serum anticholinergic and serum neuroleptic levels (r=0.16) and the ratio of serum anticholinergic to serum neuroleptic was a poor predictor of EPS (r=0.26).

The results suggest a marked variation in sensitivity of patients to the EPS-inducing of neuroleptics; nevertheless, the incidence of EPS decreases with increasing serum levels of anticholinergics. An optimal serum anticholinergic level of 10 pmole atropine equivalent per ml was associated with a low incidence of EPS and is relevant to drug action at the striatal muscarinic receptor.

Key words

Anticholinergics Extrapyramidal side effects Muscarinic receptor Neuroleptics Senizophrenia Serum drug levels 


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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Larry Tune
    • 1
    • 2
    • 3
  • Joseph T. Coyle
    • 1
    • 2
    • 3
  1. 1.Department of NeuroscienceJohns Hopkins University, School of MedicineBaltimoreUSA
  2. 2.Department of Pharmacology and Experimental TherapeuticsJohns Hopkins University, School of MedicineBaltimoreUSA
  3. 3.Department of Psychiatry and The Behavioral SciencesJohns Hopkins University, School of MedicineBaltimoreUSA

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