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
−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 [ edit ] 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 [ edit ] 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] [5]
References [ edit ]
^ "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
