Vigabatrin: effects on human brain GABA levels by nuclear magnetic resonance spectroscopy.
Vigabatrin (VGB, Sabril) is a new antiepileptic drug used for treatment of partial and secondarily generalized tonic-clonic seizures. Many controlled short- and long-term trials have established efficacy as add-on therapy. Side effects have been infrequent. VGB acts as an irreversible substrate for gamma-aminobutyric acid (GABA) transaminase that leads to elevated brain GABA levels. Although this mechanism has been confirmed in animals and in cerebrospinal fluid of humans, we report the first study of brain GABA levels using noninvasive nuclear magnetic resonance spectroscopy. GABA elevation in brain closely parallels VGB dosage and reaches concentrations 2-3 times control values at daily dosage of 3 g. This technique offers promising potential to monitor changes induced by VGB as a function of time, dose, and clinical effect.
Department of Veterans Affairs Medical Center, West Haven, CT 06516.
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RH
Mattson
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Petroff
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Rothman
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Behar
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D001923:Brain Chemistry / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013268:Stimulation, Chemical; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin