Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
The new generation of GABA enhancers - Potential in the treatment of epilepsy
Autore:
Czuczwar, SJ; Patsalos, PN;
Indirizzi:
Univ London, Pharmacol & Therapeut Unit, Dept Clin Neurol,Inst Neurol, Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England Univ London London England WC1N 3BG Neurosurg, London WC1N 3BG, England Med Univ, Dept Pathophysiol, Lublin, Poland Med Univ Lublin PolandMed Univ, Dept Pathophysiol, Lublin, Poland Inst Agr Med, Isotope Lab, Lublin, Poland Inst Agr Med Lublin PolandInst Agr Med, Isotope Lab, Lublin, Poland Chalfont Ctr Epilepsy, Chalfont St Peter, England Chalfont Ctr Epilepsy Chalfont St Peter England lfont St Peter, England
Titolo Testata:
CNS DRUGS
fascicolo: 5, volume: 15, anno: 2001,
pagine: 339 - 350
SICI:
1172-7047(2001)15:5<339:TNGOGE>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
GAMMA-AMINOBUTYRIC-ACID; ANTIEPILEPTIC DRUGS; ANTICONVULSANT ACTIVITY; BRAIN GABA; RECEPTOR ANTAGONISTS; VIGABATRIN THERAPY; STEROID MODULATOR; PARTIAL SEIZURES; HIGH-AFFINITY; WEST-SYNDROME;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
76
Recensione:
Indirizzi per estratti:
Indirizzo: Patsalos, PN Univ London, Pharmacol & Therapeut Unit, Dept Clin Neurol,Inst Neurol, Natl Hosp Neurol & Neurosurg, Queen Sq, London WC1N 3BG, England Univ London Queen Sq London England WC1N 3BG 1N 3BG, England
Citazione:
S.J. Czuczwar e P.N. Patsalos, "The new generation of GABA enhancers - Potential in the treatment of epilepsy", CNS DRUGS, 15(5), 2001, pp. 339-350

Abstract

gamma -Aminobutyric acid (GABA) is considered to be the major inhibitory neuro-transmitter in the brain and loss of GABA inhibition has been clearly implicated in epileptogenesis. GABA interacts with 3 types of receptor: GABA(A), CABA(B) and GABA(C). The GABA(A) receptor has provided an excellent target for the development of drugs with an anticonvulsant action. Some clinically useful anticonvulsants, such as the benzodiazepines and barbituratesand possibly valproic acid (sodium valproate), act at this receptor. In recent years 4 new anticonvulsants, namely vigabatrin, tiagabine, gabapentin and topiramate, with a mechanism of action considered to be primarilyvia an effect on GABA, have been licensed. Vigabatrin elevates brain GABA levels by inhibiting the enzyme GABA transaminase which is responsible for intracellular GABA catabolism. In contrast, tiagabine elevates synaptic GABA levels by inhibiting the GABA uptake transporter, GAT1, and preventing the uptake of GABA into neurons and glia. Gabapentin, a cyclic analogue of GABA, acts by enhancing GABA synthesis and also by decreasing neuronal calcium influx via a specific subunit of voltage-dependent calcium channels. Topiramate acts, in part, via an action on a novel site of the GABA(A) receptor. Although these drugs are useful in some patients, overall, they have proven to be disappointing as they have had little impact on the prognosis of patients with intractable epilepsy. Despite this, additional GABA enhancing anticonvulsants are presently under development. Ganaxolone, retigabine and pregabalin may prove to have a more advantageous therapeutic profile than the presently licensed GABA enhancing drugs. This anticipation is based on 2 characteristics. First, they actby hitherto unique mechanisms of action in enhancing GABA-induced neuronalinhibition. Secondly, they act on additional antiepileptogenic mechanisms. Finally, CGP 36742, a GABA(B) receptor antagonist, may prove to be particularly useful in the management of primary generalised absence seizures. The exact impact of these new GABA-enhancing drugs in the treatment of epilepsy will have to await their licensing and a period of postmarketing surveillance. As to clarification of their role in the management of epilepsy, this will have to await further clinical trials, particularly direct comparative trials with other anticonvulsants.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/02/20 alle ore 00:45:38