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]
Medical uses
GABOB is an anticonvulsant and is used in the treatment of epilepsy.[1][2]
Pharmacology
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]
Chemistry
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
Generic name
GABOB has been referred to by the generic name buxamine or buxamina.[1][6]
Brand names
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]
References
- ^ 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.
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Ionotropic | GABAATooltip 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 (123I)
- 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
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GABAA-ρTooltip γ-Aminobutyric acid A-rho receptor | |
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Metabotropic | GABABTooltip γ-Aminobutyric acid B receptor | - Negative modulators: Compound 14
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- See also
- Receptor/signaling modulators
- GABAA receptor positive modulators
- GABA metabolism/transport modulators
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