Selective inhibitor of Glycine transporter 1
ORG-24598
Names
IUPAC name
2-[Methyl-[(3R )-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]amino]acetic acid
Identifiers
ChEMBL
ChemSpider
InChI=1S/C19H20F3NO3/c1-23(13-18(24)25)12-11-17(14-5-3-2-4-6-14)26-16-9-7-15(8-10-16)19(20,21)22/h2-10,17H,11-13H2,1H3,(H,24,25)/t17-/m1/s1
Key: KZWQAWBTWNPFPW-QGZVFWFLSA-N
CN(CCC(C1=CC=CC=C1)OC2=CC=C(C=C2)C(F)(F)F)CC(=O)O
Properties
C 19 H 20 F 3 N O 3
Molar mass
367.368 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
ORG-24598 is a selective inhibitor of the type 1 glycine transporter .[ 1]
Potential uses
Alcohol use disorder
A test in rats has showed that combining varenicline , bupropion , and an indirect glycine agonist (such as ORG-24598) could be beneficial for treatment of alcohol use disorder .[ 2]
Schizophrenia
Studies have shown that glycine re-uptake inhibitors selective for the type 1 transporter may be useful for the treatment of certain schizophrenia symptoms.[ 3] [ 4]
References
^ "2-[methyl-[(3R)-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propyl]amino]acetic acid" . pubchem.ncbi.nlm.nih.gov . Retrieved 2024-08-17 .
^ Olsson, Yasmin; Lidö, Helga; Ademar, Karin; Cadeddu, Davide; Ericson, Mia; Söderpalm, Bo (January 2024). "The GlyT1-inhibitor Org 24598 facilitates the alcohol deprivation abolishing and dopamine elevating effects of bupropion + varenicline in rats" . Journal of Neural Transmission (Vienna, Austria: 1996) . 131 (1): 95–106. doi :10.1007/s00702-023-02701-x . ISSN 1435-1463 . PMC 10769923 . PMID 37773223 .
^ Chue, Pierre (2013). "Glycine reuptake inhibition as a new therapeutic approach in schizophrenia: focus on the glycine transporter 1 (GlyT1)" . Current Pharmaceutical Design . 19 (7): 1311–1320. doi :10.2174/138161213804805766 . ISSN 1873-4286 . PMID 23194655 .
^ Javitt, Daniel C. (July 2002). "Glycine modulators in schizophrenia" . Current Opinion in Investigational Drugs (London, England: 2000) . 3 (7): 1067–1072. ISSN 1472-4472 . PMID 12186269 .
Receptor (ligands )
GlyR Tooltip Glycine receptor
Positive modulators: Alcohols (e.g., brometone , chlorobutanol (chloretone) , ethanol (alcohol) , tert -butanol (2M2P) , tribromoethanol , trichloroethanol , trifluoroethanol )
Alkylbenzene sulfonate
Anandamide
Barbiturates (e.g., pentobarbital , sodium thiopental )
Chlormethiazole
D12-116
Dihydropyridines (e.g., nicardipine )
Etomidate
Ginseng constituents (e.g., ginsenosides (e.g., ginsenoside-Rf ))
Glutamic acid (glutamate)
Ivermectin
Ketamine
Neuroactive steroids (e.g., alfaxolone , pregnenolone (eltanolone) , pregnenolone acetate , minaxolone , ORG-20599 )
Nitrous oxide
Penicillin G
Propofol
Tamoxifen
Tetrahydrocannabinol
Triclofos
Tropeines (e.g., atropine , bemesetron , cocaine , LY-278584 , tropisetron , zatosetron )
Volatiles /gases (e.g., chloral hydrate , chloroform , desflurane , diethyl ether (ether) , enflurane , halothane , isoflurane , methoxyflurane , sevoflurane , toluene , trichloroethane (methyl chloroform) , trichloroethylene )
Xenon
Zinc
Antagonists: 2-Aminostrychnine
2-Nitrostrychnine
4-Phenyl-4-formyl-N-methylpiperidine
αEMBTL
Bicuculline
Brucine
Cacotheline
Caffeine
Colchicine
Colubrine
Cyanotriphenylborate
Dendrobine
Diaboline
Endocannabinoids (e.g., 2-AG , anandamide (AEA) )
Gaboxadol (THIP)
Gelsemine
iso-THAZ
Isobutyric acid
Isonipecotic acid
Isostrychnine
Laudanosine
N-Methylbicuculline
N-Methylstrychnine
N,N-Dimethylmuscimol
Nipecotic acid
Pitrazepin
Pseudostrychnine
Quinolines (e.g., 4-hydroxyquinoline , 4-hydroxyquinoline-3-carboxylic acid , 5,7-CIQA , 7-CIQ , 7-TFQ , 7-TFQA )
RU-5135
Sinomenine
Strychnine
Thiocolchicoside
Tutin
Negative modulators: Amiloride
Benzodiazepines (e.g., bromazepam , clonazepam , diazepam , flunitrazepam , flurazepam )
Corymine
Cyanotriphenylborate
Daidzein
Dihydropyridines (e.g., nicardipine , nifedipine , nitrendipine )
Furosemide
Genistein
Ginkgo constituents (e.g., bilobalide , ginkgolides (e.g., ginkgolide A , ginkgolide B , ginkgolide C , ginkgolide J , ginkgolide M ))
Imipramine
NBQX
Neuroactive steroids (e.g., 3α-androsterone sulfate , 3β-androsterone sulfate , deoxycorticosterone , DHEA sulfate , pregnenolone sulfate , progesterone )
Opioids (e.g., codeine , dextromethorphan , dextrorphan , levomethadone , levorphanol , morphine , oripavine , pethidine , thebaine )
Picrotoxin (i.e., picrotin and picrotoxinin )
PMBA
Riluzole
Tropeines (e.g., bemesetron , LY-278584 , tropisetron , zatosetron )
Verapamil
Zinc
NMDAR Tooltip N-Methyl-D-aspartate receptor
Transporter (blockers )
GlyT1 Tooltip Glycine transporter 1 GlyT2 Tooltip Glycine transporter 2