Psychopharmacology

, Volume 143, Issue 4, pp 347–357 | Cite as

Phenylalanine kinetics are associated with tardive dyskinesia in men but not in women

  • M. A. Richardson
  • Margaret A. Reilly
  • Laura L. Read
  • Cheryl J. Flynn
  • Raymond F. Suckow
  • Timothy J. Maher
  • Istvan Sziraki
ORIGINAL INVESTIGATION

Abstract

Rationale: An association between tardive dyskinesia (TD) and severely impaired metabolism of the large neutral amino acid (LNAA), phenylalanine (Phe) was defined in a group of mentally retarded patients. Subsequently, an altered kinetics of Phe was associated with TD in men with schizophrenia based on plasma analyses subsequent to the ingestion of a protein meal. Methods: In the present study, a standardized oral challenge of pure Phe (100 mg/kg in 170 ml orange juice) was administered to psychiatric patients of both sexes (n = 312), with and without TD after an overnight fast. Plasma LNAA levels were assayed both fasting and 2 h subsequent to the ingestion of the challenge. The extent of the increase in plasma Phe levels 2 h following a standardized challenge is determined by the sum of the kinetic processes of plasma absorption, tissue distribution, metabolism and elimination. Results: The study hypothesis, that TD would be associated with significantly higher post-challenge plasma Phe indices of an absolute plasma Phe level and plasma Phe/LNAA ratio (a brain availability measure), was verified for the study men (n = 209), but not for the study women (n = 103). Conclusions: The demonstrated altered kinetics of Phe in men with TD indicates a greater availability of Phe to the brain in these men. We suggest that the disorder may be related to the effects of this greater availability. Such effects could be the direct neurotoxic effects of Phe and its metabolites and/or the modulating effects of these compounds on the synthesis of the monoamine neurotransmitters. The fact that TD (Yes/No) group differences in post-challenge plasma Phe indices were not seen for the study women suggests the possibility of a sex difference in the biology of TD that we propose may be reflective of the young age of the study sample.

Key words Amine neurotransmitter supersensitivity Blood-brain barrier transport Gastric emptying Hepatic clearance Kinetics Large neutral amino acid Movement disorder Neuroleptic Neurotransmitter precursors Neurotransmitter synthesis Phenylalanine Plasma absorption Sex difference Tardive dyskinesia 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • M. A. Richardson
    • 1
  • Margaret A. Reilly
    • 3
  • Laura L. Read
    • 1
  • Cheryl J. Flynn
    • 1
  • Raymond F. Suckow
    • 4
  • Timothy J. Maher
    • 6
  • Istvan Sziraki
    • 3
  1. 1.Movement Disorders Division, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA Fax: +1-914-398-5518US
  2. 2.Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, NY 10016, USAUS
  3. 3.Neurochemistry Division, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USAUS
  4. 4.Psychopharmacology Division, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USAUS
  5. 5.New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, USAUS
  6. 6.Division of Pharmaceutical Sciences, The Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115, USAUS
  7. 7.Department of Brain and Cognitive Sciences, The Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USAUS
  8. 8.Division of Biochemistry, Institute for Drug Research, Budapest, HungaryHU

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