Effect of Long-Term Vigabatrin Therapy on Selected Neurotransmitter Concentrations in Cerebrospinal Fluid
| Autor: | Elinor Ben-Menachem, K.D. Haegele, N.D. Huebert, John Mumford |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Drug
genetic structures Catabolism business.industry media_common.quotation_subject Homovanillic acid Pharmacology Vigabatrin Norepinephrine (medication) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cerebrospinal fluid chemistry Dopamine 030225 pediatrics Pediatrics Perinatology and Child Health medicine Neurology (clinical) Neurotransmitter business 030217 neurology & neurosurgery medicine.drug media_common |
| Zdroj: | Journal of Child Neurology. 6:2S11-2S16 |
| ISSN: | 1708-8283 0883-0738 |
| DOI: | 10.1177/0883073891006002041 |
| Popis: | 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 γ-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. (J Child Neurol 1991;6(Suppl):2S11-2S16). |
| Databáze: | OpenAIRE |
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