Anticonvulsant drug
γ-Amino-β-hydroxybutyric acid (GABOB ), also known as β-hydroxy-γ-aminobutyric acid (β-hydroxy-GABA ), and sold under the brand name Gamibetal among others, is an anticonvulsant which is used for the treatment of epilepsy in Europe , Japan , and Mexico .[1] [2] It is a GABA analogue , or an analogue of the neurotransmitter γ-aminobutyric acid (GABA), and has been found to be an endogenous metabolite of GABA.[2] [3] [4] [5]
GABOB is an anticonvulsant and is used in the treatment of epilepsy .[1] [2]
GABOB is a GABA receptor agonist .[6] It has two stereoisomers , and shows stereoselectivity in its actions.[6] Specifically, (R )-(–)-GABOB is a moderate-potency agonist of the GABAB receptor , while (S )-(+)-GABOB is a partial agonist of the GABAB receptor and an agonist of the GABAA receptor .[6] (S )-(+)-GABOB is around twice as potent an anticonvulsant as (R )-(–)-GABOB.[7] GABOB is used medically as a racemic mixture .[6]
Relative to GABA, GABOB has more potent inhibitory effects on the central nervous system , perhaps due to its greater capacity to cross the blood–brain barrier .[5] [8] However, GABOB is of relatively low potency as an anticonvulsant when used by itself, and is more useful as an adjuvant treatment used alongside another anticonvulsant.[9] [10]
GABOB, or β-hydroxy-GABA, is a close structural analogue of GABA (see GABA analogue ), as well as of γ-hydroxybutyric acid (GHB), phenibut (β-phenyl-GABA), baclofen (β-(4-chlorophenyl)-GABA),[11] and pregabalin (β-isobutyl-GABA).
Society and culture [ edit ] GABOB has been referred to by the generic name buxamine or buxamina .[1] [6]
GABOB is sold primarily under the brand name Gamibetal.[1] It has also been marketed under a variety of other brand names including Aminoxan, Bogil, Diastal, Gabimex, Gabomade, Gaboril, Gamalate, and Kolpo.[1] [12]
^ a b c d e Index Nominum 2000: International Drug Directory . Taylor & Francis. January 2000. pp. 44–. ISBN 978-3-88763-075-1 .
^ a b c Smith MB (23 October 2013). "Biologically Important Amino Acids" . Methods of Non-α-Amino Acid Synthesis (Second ed.). CRC Press. pp. 146–. ISBN 978-1-4665-7789-3 .
^ Cooper JR, Bloom FE, Roth RH (2003). The Biochemical Basis of Neuropharmacology . Oxford University Press. pp. 112–. ISBN 978-0-19-514007-1 .
^ Melis GB, Paoletti AM, Mais V, Mastrapasqua NM, Strigini F, Fruzzetti F, et al. (2014). "Dose-related effects of gamma-amino beta-hydroxy butyric acid (GABOB) infusion on growth hormone secretion in normal women". Journal of Endocrinological Investigation . 5 (2): 101–106. doi :10.1007/BF03350499 . PMID 7096918 . S2CID 71239193 .
^ a b Hayashi T (March 1959). "The inhibitory action of beta-hydroxy-gamma-aminobutyric acid upon the seizure following stimulation of the motor cortex of the dog" . The Journal of Physiology . 145 (3): 570–578. doi :10.1113/jphysiol.1959.sp006163 . PMC 1356963 . PMID 13642322 .
^ a b c d e Corelli F, Mugnaini C (17 January 2017). "Chemistry of GABAB Receptor Ligands: Focus on Agonists and Antagonists" . In Colombo G (ed.). GABAB Receptor . Springer. pp. 25–. ISBN 978-3-319-46044-4 .
^ Roberts E, Krause DN, Wong E, Mori A (February 1981). "Different Efficacies of d- and l-γ-Amino-β-Hydroxybutyric Acids in GABA Receptor and Transport Test Systems" . The Journal of Neuroscience . 1 (2): 132–140. doi :10.1523/JNEUROSCI.01-02-00132.1981 . PMC 6564147 . PMID 6267220 .
^ Demaio D, Pasquariello G (October 1963). "Gamma-amino-beta-hydroxybutyric acid (GABOB) and brain serotonin". Psychopharmacologia . 5 (1): 84–86. doi :10.1007/BF00405577 . PMID 14085623 . S2CID 1436623 .
^ Chemello R, Giaretta D, Pellegrini A, Testa G (1980). "[Effect of gamma-amino-beta-hydroxybutyric acid (GABHB) on experimentally-induced epileptic activity]" [Effect of γ-amino-β-hydroxybutyric acid (GABHB) on experimentally-induced epileptic activity]. Rivista di Neurologia (in Italian). 50 (4): 253–268. PMID 7466221 .
^ García-Flores E, Farías R (1997). "gamma-Amino-beta-hydroxybutyric acid as add-on therapy in adult patients with severe focal epilepsy". Stereotactic and Functional Neurosurgery . 69 (1-4 Pt 2): 243–246. doi :10.1159/000099882 . PMID 9711762 .
^ Lapin I (2001). "Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug" . CNS Drug Reviews . 7 (4): 471–481. doi :10.1111/j.1527-3458.2001.tb00211.x . PMC 6494145 . PMID 11830761 .
^ Muller NF (19 June 1998). European Drug Index: European Drug Registrations (Fourth ed.). CRC Press. pp. 181–. ISBN 978-3-7692-2114-5 .
Ionotropic
GABAA Tooltip γ-Aminobutyric acid A receptor
Positive modulators (abridged; see here for a full list): α-EMTBL
Alcohols (e.g., drinking alcohol , 2M2B )
Anabolic steroids
Avermectins (e.g., ivermectin )
Barbiturates (e.g., phenobarbital )
Benzodiazepines (e.g., diazepam )
Bromide compounds (e.g., potassium bromide )
Carbamates (e.g., meprobamate )
Carbamazepine
Chloralose
Chlormezanone
Clomethiazole
Dihydroergolines (e.g., ergoloid (dihydroergotoxine) )
Etazepine
Etifoxine
Fenamates (e.g., mefenamic acid )
Flavonoids (e.g., apigenin , hispidulin )
Fluoxetine
Flupirtine
Imidazoles (e.g., etomidate )
Kava constituents (e.g., kavain )
Lanthanum
Loreclezole
Monastrol
Neuroactive steroids (e.g., allopregnanolone , cholesterol , THDOC )
Niacin
Niacinamide
Nonbenzodiazepines (e.g., β-carbolines (e.g., abecarnil ), cyclopyrrolones (e.g., zopiclone ), imidazopyridines (e.g., zolpidem ), pyrazolopyrimidines (e.g., zaleplon ))
Norfluoxetine
Petrichloral
Phenols (e.g., propofol )
Phenytoin
Piperidinediones (e.g., glutethimide )
Propanidid
Pyrazolopyridines (e.g., etazolate )
Quinazolinones (e.g., methaqualone )
Retigabine (ezogabine)
ROD-188
Skullcap constituents (e.g., baicalin )
Stiripentol
Sulfonylalkanes (e.g., sulfonmethane (sulfonal) )
Topiramate
Valerian constituents (e.g., valerenic acid )
Volatiles /gases (e.g., chloral hydrate , chloroform , diethyl ether , paraldehyde , sevoflurane )
Negative modulators: 1,3M1B
3M2B
11-Ketoprogesterone
17-Phenylandrostenol
α3IA
α5IA (LS-193,268)
β-CCB
β-CCE
β-CCM
β-CCP
β-EMGBL
Anabolic steroids
Amiloride
Anisatin
β-Lactams (e.g., penicillins , cephalosporins , carbapenems )
Basmisanil
Bemegride
Bicyclic phosphates (TBPS , TBPO , IPTBO )
BIDN
Bilobalide
Bupropion
CHEB
Chlorophenylsilatrane
Cicutoxin
Cloflubicyne
Cyclothiazide
DHEA
DHEA-S
Dieldrin
(+)-DMBB
DMCM
DMPC
EBOB
Etbicyphat
FG-7142 (ZK-31906)
Fiproles (e.g., fipronil )
Flavonoids (e.g., amentoflavone , oroxylin A )
Flumazenil
Fluoroquinolones (e.g., ciprofloxacin )
Flurothyl
Furosemide
Golexanolone
Iomazenil (123 I)
IPTBO
Isopregnanolone (sepranolone)
L-655,708
Laudanosine
Lindane
MaxiPost
Morphine
Morphine-3-glucuronide
MRK-016
Naloxone
Naltrexone
Nicardipine
Nonsteroidal antiandrogens (e.g., apalutamide , bicalutamide , enzalutamide , flutamide , nilutamide )
Oenanthotoxin
Pentylenetetrazol (pentetrazol)
Phenylsilatrane
Picrotoxin (i.e., picrotin , picrotoxinin and dihydropicrotoxinin )
Pregnenolone sulfate
Propybicyphat
PWZ-029
Radequinil
Ro 15-4513
Ro 19-4603
RO4882224
RO4938581
Sarmazenil
SCS
Suritozole
TB-21007
TBOB
TBPS
TCS-1105
Terbequinil
TETS
Thujone
U-93631
Zinc
ZK-93426
GABAA -ρ Tooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABAB Tooltip γ-Aminobutyric acid B receptor
Negative modulators: Compound 14