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Benzodiazepine antagonist
Ro 19-4603
[1]
Names
IUPAC name
tert -Butyl 8-methyl-7-oxo-5-thia-1,8,12-triazatricyclo[8.3.0.02,6 ]trideca-2(6),3,10,12-tetraene-11-carboxylate
Identifiers
ChEBI
ChEMBL
ChemSpider
KEGG
InChI=1S/C15H17N3O3S/c1-15(2,3)21-14(20)11-10-7-17(4)13(19)12-9(5-6-22-12)18(10)8-16-11/h5-6,8H,7H2,1-4H3
Key: ZIGMMUKDYCABPW-UHFFFAOYSA-N
CC(C)(C)OC(=O)C1=C2CN(C(=O)C3=C(N2C=N1)C=CS3)C
Properties
C 15 H 17 N 3 O 3 S
Molar mass
319.38 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Ro 19-4603 is an
inverse agonist of the benzodiazepine binding site. It has effects antagonistic to those of benzodiazepines.
Chemistry
Despite acting at the
benzodiazepine site , it does not possess the
benzodiazepine struture. It is an
Imidazothienodiazepine : a
thiophene ring , an
imidazole ring and a
diazepine ring fused together.
Effects & Pharmacodynamics
Ro 19-4603 is an inverse agonist at the benzodiazepine binding site. Due to this, it has effects similar to other benzodiazepine inverse agonists, notably:
anxiogenesis ,
[2]
convulsions .
[3]
Administration of this compound was able to decrease voluntary alcohol consumption. This was also observed in rats selected for high alcohol preference.
[4] In addition to decreasing its consumption, Ro 19-4603 is able to antagonize the intoxicating effects of alcohol.
[5]
References
^
"Tert-butyl 5-methyl-6-oxo-5,6-dihydro-4h-imidazo[1,5-a]thieno[2,3-f][1,4]diazepine-3-carboxylate" .
^ Belzung, C.; Misslin, R.; Vogel, E. (July 1990).
"Anxiogenic effects of a benzodiazepine receptor partial inverse agonist, RO 19-4603, in a light/dark choice situation" . Pharmacology, Biochemistry, and Behavior . 36 (3): 593–596.
doi :
10.1016/0091-3057(90)90260-o .
ISSN
0091-3057 .
PMID
2165618 .
S2CID
9881393 .
^ Kubová, H.; Mares, P. (October 1994).
"Convulsant action of a benzodiazepine receptor agonist/inverse agonist Ro 19-4603 in developing rats" . Naunyn-Schmiedeberg's Archives of Pharmacology . 350 (4): 393–397.
doi :
10.1007/BF00178957 .
ISSN
0028-1298 .
PMID
7845475 .
S2CID
1751486 .
^ Balakleevsky, A.; Colombo, G.; Fadda, F.; Gessa, G. L. (1990).
"Ro 19-4603, a benzodiazepine receptor inverse agonist, attenuates voluntary ethanol consumption in rats selectively bred for high ethanol preference" . Alcohol and Alcoholism (Oxford, Oxfordshire) . 25 (5): 449–452.
ISSN
0735-0414 .
PMID
1965120 .
^ Lister, R. G.; Durcan, M. J. (1989-03-13).
"Antagonism of the intoxicating effects of ethanol by the potent benzodiazepine receptor ligand Ro 19-4603" . Brain Research . 482 (1): 141–144.
doi :
10.1016/0006-8993(89)90551-9 .
ISSN
0006-8993 .
PMID
2539880 .
S2CID
22770686 .
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