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 .
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
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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