• Michael E Henry, J Eric Jensen, Stephanie C Licata, Caitlin Ravichandran, Michelle L Butman, Meghan Shanahan, Tara L Lauriat, and Perry F Renshaw.
• Caritas St. Elizabeth's Medical Center, Department of Psychiatry, Boston, MA 02135, USA. michael.henry@caritaschristi.org
• Psychiatry Res. 2010 Dec 30;184(3):171-6.

AbstractBenzodiazepines (BZs), which are typically used as anxiolytics, act by modulating inhibitory signaling through gamma-aminobutyric acid A (GABA)(A) receptors. Functionally, the inhibitory effects of GABA may be counterbalanced by the excitatory effects of glutamate (Glu) as the two neurotransmitter systems are metabolically linked through their synthetic intermediate glutamine (Gln). The primary aim of this study was to determine whether the effects of different BZs on the GABA and Glu/Gln systems would vary according to the pharmacokinetics of the different drugs. Proton magnetic resonance spectroscopy ((1)H MRS) was used to measure GABA, Glu, and Gln levels in six healthy adult volunteers 1h and 10 h following immediate release alprazolam, extended release alprazolam, clonazepam, or placebo. Although there were no differences between 1 and 10 h when the drugs were examined individually, there was a trend level difference between the 1- and 10-h effects of BZs on Gln when the BZs were combined. In post-hoc comparisons, the difference in the Gln to creatine (Cr) ratio was 0.04 for the BZs versus placebo at 1h and 0.01 at 10h following the administration of drug (t(11)=2.49, P=0.03 1 h; t(10)=0.65, P=0.53 10 h; no correction for multiple comparisons). An increase in Gln/Cr at 1 h post-BZ is consistent with a functionally synergistic relationship between Glu/Gln and GABA in the brain. It also suggests that MRS may have sufficient sensitivity to detect acute drug effects.Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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