Page last updated: 2024-11-10

loreclezole

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

loreclezole: RN given for Z-isomer; RN for cpd without isomeric designation not avail 12/90 [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID3034012
CHEMBL ID1397886
CHEBI ID92491
SCHEMBL ID567973
MeSH IDM0182321

Synonyms (41)

Synonym
r-72063
loreclezole
NCGC00025098-01
tocris-1295
loreclezole (usan/inn)
D04780
117857-45-1
loreclezolum [inn-latin]
r 72063
loreclezol [inn-spanish]
1h-1,2,4-triazole, 1-(2-chloro-2-(2,4-dichlorophenyl)ethenyl)-, (z)-
(z)-1-(beta,2,4-trichlorostyryl)-1h-1,2,4-triazole
1-[(z)-2-chloro-2-(2,4-dichlorophenyl)ethenyl]-1,2,4-triazole
CHEMBL1397886
unii-6dj32stz5w
loreclezol
6dj32stz5w ,
loreclezolum
loreclezole [usan:inn:ban]
gtpl5466
1-[(z)-2-chloro-2-(2,4-dichlorophenyl)ethenyl]-1h-1,2,4-triazole
loreclezole [usan]
loreclezole [inn]
SCHEMBL567973
DTXSID6048252
1-[(z)-2-chloro-2-(2,4-dichlorophenyl)ethenyl]-1h-1,2,4-triazole #
XGLHZTBDUXXHOM-WMZJFQQLSA-N
(z)-1-(.beta.,2,4-trichlorostyryl)-1h-1,2,4-triazole
AKOS028112291
1h-1,2,4-triazole, 1-[(1z)-2-chloro-2-(2,4-dichlorophenyl)ethenyl]-
CHEBI:92491
bdbm50503422
(z)-1-(2-chloro-2-(2,4-dichlorophenyl)ethenyl)-(1h)-1,2,4-triazolehydrochloride
(z)-1-(2-chloro-2-(2,4-dichlorophenyl)vinyl)-1h-1,2,4-triazole
BS-14505
HY-105272
Q6680282
117857-45-1 (free base)
CS-0025565
D80761
1h-1,2,4-triazole,1-[(1z)-2-chloro-2-(2,4-dichlorophenyl)ethenyl]-

Research Excerpts

Overview

Loreclezole is a novel antiepileptic that interacts in a unique way with the GABAA receptor complex. It has been reported to potentiate GABA via a novel allosteric site on the beta-subunit of the receptor.

ExcerptReferenceRelevance
"Loreclezole is an experimental anticonvulsant drug. "( The anticonvulsant effect of the broad spectrum anticonvulsant loreclezole may be mediated in part by serotonin in rats: a microdialysis study.
Dailey, JW; Jo, M; Jobe, PC; Ko, KH; Seo, DO; Yan, QS, 1994
)
1.97
"Loreclezole is a novel antiepileptic that interacts in a unique way with the GABAA receptor complex. "( Lack of effect of flumazenil and CGS 8216 on the anxiolytic-like properties of loreclezole.
Bayley, P; Curnow, R; Dawson, GR; Rambridge, A; Tricklebank, MD, 1994
)
1.96
"Loreclezole is a newly developed antiepileptic drug which has been shown to act at a specific site on beta 2 or beta 3 GABAA receptor subtypes to enhance the peak whole-cell response to submaximal concentrations of GABA. "( Loreclezole enhances apparent desensitization of recombinant GABAA receptor currents.
Donnelly, JL; MacDonald, RL, 1996
)
3.18
"Loreclezole is an anticonvulsant and anxiolytic compound which has been reported to potentiate GABA via a novel allosteric site on the beta-subunit of the receptor. "( A behavioural and neurochemical study in rats of the pharmacology of loreclezole, a novel allosteric modulator of the GABAA receptor.
Cross, AJ; Green, AR; Misra, A; Murray, TK; Snape, MF, 1996
)
1.97

Toxicity

ExcerptReferenceRelevance
" During the trial, only mild adverse events were reported in both the loreclezole and the placebo group, nor were any clinically relevant abnormalities seen in the haematological and biochemical analysis."( A double-blind, placebo-controlled evaluation of the efficacy and safety of loreclezole as add-on therapy in patients with uncontrolled partial seizures.
de Beukelaar, F; Hulsman, J; Janssen, A; Meijer, J; Overweg, J; Rentmeester, T; Scholtes, F; van der Kleij, B,
)
0.59

Pharmacokinetics

ExcerptReferenceRelevance
" However, these combinations were associated with significant pharmacokinetic interactions, in that LCZ increased brain TPM (94%), OXC (21%), FBM (46%), and LTG (8%) concentrations."( Pharmacodynamic and pharmacokinetic interaction studies of loreclezole with felbamate, lamotrigine, topiramate, and oxcarbazepine in the mouse maximal electroshock seizure model.
Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2005
)
0.57
" However, these conclusions are confounded by the fact that LCZ is associated with significant pharmacokinetic interactions."( Pharmacodynamic and pharmacokinetic interaction studies of loreclezole with felbamate, lamotrigine, topiramate, and oxcarbazepine in the mouse maximal electroshock seizure model.
Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2005
)
0.57
" Any pharmacokinetic contribution was ascertained by measurement of brain antiepileptic drug (AED) concentrations."( Pharmacodynamic and/or pharmacokinetic characteristics of interactions between loreclezole and four conventional antiepileptic drugs in pentylenetetrazole-induced seizures in mice: an isobolographic analysis.
Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N, 2005
)
0.56

Dosage Studied

Loreclezole was dosed to reach a target plasma concentration between 1 and 3 mg/l. We determined anticonvulsant dose-response relationships in genetically epilepsy-prone rats (GEPRs)

ExcerptRelevanceReference
" Loreclezole was dosed to reach a target plasma concentration between 1 and 3 mg/l."( Efficacy and safety evaluation of loreclezole as add-on treatment in therapy-resistant epilepsy patients.
Hulsman, J; Rentmeester, T, 1991
)
1.47
" To determine if anticonvulsant doses of loreclezole increase extracellular serotonin, we determined anticonvulsant dose-response relationships in genetically epilepsy-prone rats (GEPRs)."( The anticonvulsant effect of the broad spectrum anticonvulsant loreclezole may be mediated in part by serotonin in rats: a microdialysis study.
Dailey, JW; Jo, M; Jobe, PC; Ko, KH; Seo, DO; Yan, QS, 1994
)
0.79
" The enhancement of [3H]flunitrazepam binding to the benzodiazepine receptor by loreclezole as well as the effect of loreclezole on CL218872/[3H]flunitrazepam dose-response curves suggest that loreclezole does not act through the benzodiazepine site on the GABAA receptor complex, nor does it selectively modulate benzodiazepine receptor subtypes."( Loreclezole modulates [35S]t-butylbicyclophosphorothionate and [3H]flunitrazepam binding via a distinct site on the GABAA receptor complex.
Friend, JM; Gee, KW; Xue, BG, 1996
)
1.96
" Reduced efficacy against amygdala-kindled seizures, both acutely and over a 13-day chronic dosing study, was also observed in beta2N265S mice."( The role of GABAbeta2 subunit-containing receptors in mediating the anticonvulsant and sedative effects of loreclezole.
Davies, A; Groves, JO; Guscott, MR; Hallett, DJ; Pike, A; Reynolds, DS; Rosahl, TW; Wafford, KA, 2006
)
0.55
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (25)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Microtubule-associated protein tauHomo sapiens (human)Potency44.66840.180013.557439.8107AID1460
aldehyde dehydrogenase 1 family, member A1Homo sapiens (human)Potency39.81070.011212.4002100.0000AID1030
thyroid stimulating hormone receptorHomo sapiens (human)Potency15.84890.001318.074339.8107AID926; AID938
15-hydroxyprostaglandin dehydrogenase [NAD(+)] isoform 1Homo sapiens (human)Potency14.12540.001815.663839.8107AID894
cytochrome P450 3A4 isoform 1Homo sapiens (human)Potency0.31620.031610.279239.8107AID884; AID885
lethal factor (plasmid)Bacillus anthracis str. A2012Potency31.62280.020010.786931.6228AID912
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
GABA theta subunitRattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)Potency0.31621.000012.224831.6228AID885
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)EC50 (µMol)11.00000.00112.000910.0000AID1513957
Gamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)EC50 (µMol)11.00000.00141.957810.0000AID1513957
Gamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)EC50 (µMol)11.00000.00301.65329.8000AID1513957
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (12)

Processvia Protein(s)Taxonomy
gamma-aminobutyric acid signaling pathwayGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
synaptic transmission, GABAergicGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
chloride transmembrane transportGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
inhibitory synapse assemblyGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
regulation of postsynaptic membrane potentialGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
gamma-aminobutyric acid signaling pathwayGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
post-embryonic developmentGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
adult behaviorGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
synaptic transmission, GABAergicGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
cellular response to histamineGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
chloride transmembrane transportGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
inhibitory synapse assemblyGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
regulation of postsynaptic membrane potentialGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
signal transductionGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
gamma-aminobutyric acid signaling pathwayGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
synaptic transmission, GABAergicGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
roof of mouth developmentGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
cellular response to histamineGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
chloride transmembrane transportGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
inhibitory synapse assemblyGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
chemical synaptic transmissionGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
regulation of membrane potentialGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (9)

Processvia Protein(s)Taxonomy
GABA receptor activityGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potentialGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
chloride channel activityGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
benzodiazepine receptor activityGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
chloride channel activityGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
protein bindingGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potentialGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
chloride channel activityGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
neurotransmitter receptor activityGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
benzodiazepine receptor activityGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
GABA-A receptor activityGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
GABA-gated chloride ion channel activityGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
identical protein bindingGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
chloride channel activityGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
neurotransmitter receptor activityGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (13)

Processvia Protein(s)Taxonomy
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
cytoplasmic vesicle membraneGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
GABA-ergic synapseGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
postsynaptic specialization membraneGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
GABA-A receptor complexGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
chloride channel complexGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
GABA receptor complexGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
dendrite membraneGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
postsynapseGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
synapseGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
neuron projectionGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
transmembrane transporter complexGamma-aminobutyric acid receptor subunit alpha-1Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
axonGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
cytoplasmic vesicle membraneGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
dendrite membraneGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
GABA-ergic synapseGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
postsynaptic specialization membraneGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
GABA-A receptor complexGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
chloride channel complexGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
neuron projectionGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
dendrite membraneGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
synapseGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
transmembrane transporter complexGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
postsynapseGamma-aminobutyric acid receptor subunit gamma-2Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
cytoplasmic vesicle membraneGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
postsynaptic specialization membraneGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
GABA-A receptor complexGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
chloride channel complexGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
neuron projectionGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
synapseGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
transmembrane transporter complexGamma-aminobutyric acid receptor subunit beta-3Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (5)

Assay IDTitleYearJournalArticle
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1513957Positive allosteric modulation of GABA-A alpha1beta3gamma2S receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as increase in GABA-induced chloride current after 15 mins at -70 mV holding potential by two-microelectrode voltage clamp m
AID1513956Positive allosteric modulation of GABA-A alpha1beta3gamma2S receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as increase in GABA-induced chloride current at 100 uM after 5 mins at -70 mV holding potential by two-microelectrode voltag
AID1513955Positive allosteric modulation of GABA-A alpha1beta3gamma2S receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as increase in GABA-induced chloride current at 30 uM after 5 mins at -70 mV holding potential by two-microelectrode voltage
AID1513958Positive allosteric modulation of GABA-A alpha1beta3gamma2S receptor (unknown origin) expressed in Xenopus laevis oocytes assessed as increase in GABA-induced chloride current up to 100 uM after 15 mins at -70 mV holding potential by two-microelectrode vo
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (62)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's35 (56.45)18.2507
2000's23 (37.10)29.6817
2010's3 (4.84)24.3611
2020's1 (1.61)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 21.72

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index21.72 (24.57)
Research Supply Index4.25 (2.92)
Research Growth Index4.33 (4.65)
Search Engine Demand Index23.28 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (21.72)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials2 (2.99%)5.53%
Reviews3 (4.48%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other62 (92.54%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]