Effect of long-term vigabatrin therapy on selected neurotransmitter concentrations in cerebrospinal fluid.
Ten patients, suffering from drug-resistant complex partial seizures were treated for a period of up to 3 years with vigabatrin (Sabril). Vigabatrin is a novel antiepileptic agent, whose action is based on the inhibition of gamma-aminobutyric acid (GABA) aminotransferase, the enzyme responsible for the catabolism of the neurotransmitter GABA. Samples of lumbar cerebrospinal fluid were obtained from the patients prior to commencing vigabatrin therapy, and thereafter at 6 months, 1 year, 2 years, and up to 3 years following the initiation of vigabatrin treatment. The influence of vigabatrin on the cerebrospinal fluid concentrations of free and total GABA, homocarnosine, homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol, as well as of the drug itself, was assessed. All patients demonstrated a clinical response to vigabatrin, and the drug was well tolerated over the entire observation period. Mean (+/- SD) reduction of seizure frequency was 65% +/- 23% (range, 26% to 100%) when comparing the end of the treatment period to the previgabatrin baseline. The cerebrospinal fluid concentrations of both free and total GABA and of the dipeptide homocarnosine showed approximately 2- to 5-fold increases over baseline values, with free GABA and homocarnosine being the more sensitive variables. Cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were not altered in a significant manner over the observation period. These findings support the concept that the effects of vigabatrin are restricted to an effect on GABA catabolism and do not extend to the neurotransmitters dopamine and norepinephrine. Clinical efficacy and elevation of GABA and homocarnosine concentration were sustained over the period of observation.
Ben-Menachem
E
E
Department of Neurology, Sahlgrenska Hospital, Gothenburg, Sweden.
Persson
L I
LI
Mumford
J
J
Haegele
K D
KD
Huebert
N
N
D000328:Adult; D000614:Aminocaproates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002336:Carnosine / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D004569:Electroencephalography / Q000187:drug effects; D017029:Epilepsy, Complex Partial / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008134:Long-Term Care; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid*
D000614:Aminocaproates; D000927:Anticonvulsants; C005038:homocarnosine; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D002336:Carnosine; D020888:Vigabatrin; D006719:Homovanillic Acid