Topiramate raises anterior cingulate cortex glutamine levels in healthy men; a 4.0 T magnetic resonance spectroscopy study

Abstract

Potential mechanisms of action of topiramate include alterations of glutamatergic and GABAergic systems. In particular, topiramate has been shown to increase occipital cortex GABA levels, as measured using proton magnetic resonance spectroscopy (MRS). The purpose of this study was to measure the effect of acute oral topiramate on the GABA precursors glutamate and glutamine in the anterior cingulate cortex (ACC) and occipital lobe (OL) using high-field (4.0 T) proton MRS (1H MRS). Proton MR spectra were acquired from healthy men at three times: at baseline and 2 and 6 h after ingesting 50 (N=5) or 100 mg (N=5) of topiramate. Blood samples were acquired prior to each scan for the purpose of obtaining serum topiramate levels. A 100-mg dose of topiramate significantly increased ACC glutamine levels within 2 h of ingestion and OL glutamine levels within 6 h of ingestion. There were no measured significant effects of topiramate on ACC or OL glutamate levels. A 100-mg dose of oral topiramate increased serum topiramate and ACC glutamine levels within 2 h. OL glutamine levels increased within 6 h. Increased brain glutamine levels may be a consequence of topiramate positively modulating GABAA receptors. This result is of interest given the possible role for topiramate in the treatment of epilepsy, migraine headache, bipolar disorder, eating disorders, and alcohol dependence.