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Chemical compound
Ro4938581
3-Bromo-10-(difluoromethyl)-9H -benzo[f ]imidazo[1,5-a ][1,2,4]triazolo[1,5-d ][1,4]diazepine
CAS Number
PubChem
CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
Formula C 13 H 8 Br F 2 N 5
Molar mass 352.143 g·mol−1 3D model (
JSmol )
FC(F)C(N=C1)=C(N1C2=C3C=C(Br)C=C2)CN4C3=NC=N4
InChI=1S/C13H8BrF2N5/c14-7-1-2-9-8(3-7)13-17-5-19-21(13)4-10-11(12(15)16)18-6-20(9)10/h1-3,5-6,12H,4H2
Key:AFJRYPJIKHMNGL-UHFFFAOYSA-N
Ro4938581 is a
nootropic
drug invented in 2009 by a team working for
Hoffmann-La Roche , which acts as a subtype-selective
inverse agonist at the
α5 subtype of the
benzodiazepine binding site on the
GABAA
receptor . It has good selectivity for the α5 subtype and did not produce
convulsant or
anxiogenic effects in animal studies, making it a promising potential nootropic.
[1]
[2]
[3] Ro4938581 and a related derivative
basmisanil (RG-1662, RO5186582) have subsequently been investigated for the alleviation of
cognitive dysfunction in
Down syndrome .
[4]
[5]
See also
References
^ Ballard TM, Knoflach F, Prinssen E, Borroni E, Vivian JA, Basile J, et al. (January 2009). "RO4938581, a novel cognitive enhancer acting at GABAA alpha5 subunit-containing receptors". Psychopharmacology . 202 (1–3): 207–23.
doi :
10.1007/s00213-008-1357-7 .
PMID
18936916 .
S2CID
22011375 .
^ Knust H, Achermann G, Ballard T, Buettelmann B, Gasser R, Fischer H, et al. (October 2009). "The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive dysfunction". Bioorganic & Medicinal Chemistry Letters . 19 (20): 5940–4.
doi :
10.1016/j.bmcl.2009.08.053 .
PMID
19762240 .
^ Redrobe JP, Elster L, Frederiksen K, Bundgaard C, de Jong IE, Smith GP, et al. (June 2012). "Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats". Psychopharmacology . 221 (3): 451–68.
doi :
10.1007/s00213-011-2593-9 .
PMID
22124672 .
S2CID
2550795 .
^ Martínez-Cué C, Martínez P, Rueda N, Vidal R, García S, Vidal V, et al. (February 2013).
"Reducing GABAA α5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome" . The Journal of Neuroscience . 33 (9): 3953–66.
doi :
10.1523/JNEUROSCI.1203-12.2013 .
PMC
6619314 .
PMID
23447605 .
^ Breindl A (2019).
"Inhibiting Inhibition to Treat Down Syndrome Symptoms" . BioWorld .
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