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Science 16 July 1982:
Vol. 217. no. 4556, pp. 250 - 252
DOI: 10.1126/science.7089562
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Articles

Science, Vol 217, Issue 4556, 250-252
Copyright © 1982 by American Association for the Advancement of Science

articles

Antidepressants alter cerebrovascular permeability and metabolic rate in primates

SH Preskorn, ME Raichle, and BK Hartman

External detection of the annihilation radiation produced by water labeled with oxygen-15 was used to measure cerebrovascular permeability and cerebral blood flow in six rhesus monkeys. Use of oxygen-15 also permitted assessment of cerebral metabolic rate in two of the monkeys. Amitriptyline produced a dose-dependent, reversible increase in permeability at plasma drug concentrations which are therapeutic for depressed patients. At the same concentrations the drug also produced a 20 to 30 percent reduction in cerebral metabolic rate. At higher doses normal autoregulation of cerebral blood flow was suspended, but responsivity to arterial carbon dioxide was normal.


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P-glycoprotein reduces the ability of amitriptyline metabolites to cross the blood brain barrier in mice after a 10-day administration of amitriptyline.
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Cerebral Blood Flow and Metabolism in Late-Life Depression and Dementia.
M. S. Nobler, G. H. Pelton, and H. A. Sackeim (1999)
J Geriatr Psychiatry Neurol 12, 118-127
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Regional Cerebral Blood Flow in Mood Disorders, III: Treatment and Clinical Response.
M. S. Nobler, H. A. Sackeim, I. Prohovnik, J. R. Moeller, S. Mukherjee, D. B. Schnur, J. Prudic, and D. P. Devanand (1994)
Arch Gen Psychiatry 51, 884-897
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