The GABA shunt: an attractive and potential therapeutic target in the treatment of epileptic disorders.
Epilepsy is the most common primary neurological disorder known. Epileptiform neurons undergo paroxysmal depolarization shifts (PDS), which result in the excessive sustained neuronal firing seen in epilepsy. These shifts are due to either an impairment of GABA mediated inhibition, or an enhancement of aspartate or glutamate mediated excitatory transmission. Recent research has focused on the cellular biology of seizures. 4-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter of mammalian central nervous system. In neural and nonneural tissues, GABA is metabolized by three enzymes-glutamic acid decarboxylase (GAD), which produces GABA from glutamic acid, and the catabolic enzymes GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). Production of succinic acid by SSADH allows entry of the GABA carbon skeleton into the tricarboxylic acid cycle. GABA-T is present in a variety of circulating cells, including platelets and lymphocytes. SSADH, the final enzyme of GABA catabolism, has been detected in some of the tissues in which GAD and GABA-T have been identified. This paper is aimed at elucidating the organization of the GABA shunt and covers a review on the antiepileptic drugs, both established and currently under development targeted to the GABA shunt in order to bring about effective seizure control.
Yogeeswari
P
P
Medicinal Chemistry Research Laboratory, Pharmacy group, Birla Institute of Technology and Science, Pilani 333031, India. pyogee@bits-pilani.ac.in
Sriram
D
D
Vaigundaragavendran
J
J
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid