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Effects of Gabapentin on Brain GABA, Homocarnosine, and Pyrrolidinone in Epilepsy Patients
Author(s) -
Petroff Ognen A. C.,
Hyder Fahmeed,
Rothman Douglas L.,
Mattson Richard H.
Publication year - 2000
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.2000.tb00227.x
Subject(s) - gabapentin , vigabatrin , epilepsy , anticonvulsant , medicine , dosing , in vivo , anesthesia , pharmacology , biology , psychiatry , pathology , alternative medicine , microbiology and biotechnology
Summary:Purpose : Gabapentin (GBP) was introduced as an antiepileptic drug (AED) and has been used in the management of neuropathic pain. We reported that daily dosing increased brain γ‐aminobutyric acid (GABA) in patients with epilepsy. This study was designed to determine how rapidly brain GABA and the GABA metabolites, homocarnosine and pyrrolidinone, increase in response to the first dose of GBP. Methods : In vivo measurements of GABA, homocarnosine, and pyrrolidinone were made of a 14‐cc volume in the occipital cortex by using a 1 H spectroscopy with a 2.1‐Tesla magnetic resonance spectrometer and an 8‐cm surface coil. Six patients (four women) were studied serially after the first oral dose (1,200 mg) of GBP. Five patients (three women) taking a standard daily dose (range, 1,200–2,000 mg) of GBP were rechal‐lenged with a single high dose (2,400 mg). Results : The first dose of GBP increased median brain GABA by 1.3 m M (range, 0.4–1.8 m M ) within 1 h. Homocarnosine and pyrrolidinone did not change significantly by 5 h. Daily GBP therapy increased GABA (0.5 m M ;95% CI, 0.2–0.9), homocarnosine (0.3 m M ; 95% CI, 0.2–0.4), and pyrrolidinone (0.10 m M ; 95% CI, 0.06–0.14). Rechallenging patients taking GBP daily increased median brain GABA by 0.4 m M (range, 0.3–0.5) within 1 h. Conclusions : GBP promptly elevates brain GABA and presumably offers partial protection against further seizures within hours of the first oral dose. Patients may expect to experience the anticonvulsant effects of increased homocarnosine and pyrrolidinone with daily therapy.