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Regional brain glucose metabolism after acute alpha 2-blockade by idazoxan
M E Schmidt1, J A Matochik, R C Risinger
1Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892, USA.
Background:
Several classes of antidepressant drugs act on alpha 2-adrenergic receptors. Studies of patients with disorders responsive to treatment with these drugs report group differences in ex vivo measures of alpha 2-binding and in vivo responses mediated by alpha 2-receptors. Measurement of regional brain metabolic response to an alpha 2-antagonist may be a useful method for further definition of the role alpha 2-receptor regulation plays in the treatment of neuropsychiatric disorders.
Methods:
Regional brain glucose metabolism was measured before and after infusion with 200 micrograms/kg idazoxan with use of 18F-fluoro-2-deoxyglucose positron emission tomography in 13 healthy men. Arterial drug concentration, behavioral responses, and cardiovascular responses were also measured.
Results:
The absolute and normalized glucose metabolic rate significantly increased in primary visual cortex. Significant increases and decreases occurred in normalized metabolic rates in prefrontal cortical regions. Measurement of metabolic effects occurred during the peak cardiovascular response.
Conclusions:
Our findings are consistent with regionally specific effects of alpha 2-blockade. This method may be useful for the study of alpha 2-receptor function in humans.