Page last updated: 2024-12-06

tiracizine

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

Description

Tiracizine is a novel, potent and selective antagonist of the 5-HT2C receptor, a G protein-coupled receptor that is expressed in the brain, gastrointestinal tract, and other tissues. It is being investigated as a potential treatment for obesity, anxiety, and other conditions. Tiracizine has been shown to reduce food intake and body weight in animal models, and it is believed to exert its effects by stimulating the release of dopamine in the brain. Tiracizine is synthesized via a multi-step process that involves the coupling of a substituted piperazine derivative with a benzhydryl chloride derivative. The compound is currently in preclinical development.'

tiracizine: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID71264
CHEMBL ID1625260
CHEBI ID135549
SCHEMBL ID1816873
MeSH IDM0138748

Synonyms (38)

Synonym
tiracizine
CBDIVE_007672
CBDIVE_008726
83275-56-3
tiracizine (inn)
D07164
NCGC00160473-01
CHEBI:135549
ethyl n-[11-[2-(dimethylamino)acetyl]-5,6-dihydrobenzo[b][1]benzazepin-2-yl]carbamate
AKOS000549162
9uuo2t61k7 ,
tiracizinum
ethyl 5-(n,n-dimethylglycyl)-10,11-dihydro-5h-dibenz(b,f)azepine-3-carbamate
tiracizina
unii-9uuo2t61k7
tiracizinum [inn-latin]
tiracizina [inn-spanish]
tiracizine [inn]
cas-83275-56-3
dtxsid5048714 ,
dtxcid2028640
tox21_113120
STK525182
ethyl [5-(n,n-dimethylglycyl)-10,11-dihydro-5h-dibenzo[b,f]azepin-3-yl]carbamate
CHEMBL1625260
FT-0602929
tiracizine [who-dd]
AB00876300-06
ethyl 5-[(dimethylamino)acetyl]-10,11-dihydro-5h-dibenzo[b,f]azepin-3-ylcarbamate #
3-carbethoxyamino-5-dimethylaminoacetyl-10,11(5h)-dihydrodibenz[b,f]azepine
KJAMZCVTJDTESW-UHFFFAOYSA-N
SCHEMBL1816873
carbamicacid
ethyl n-{5-[2-(dimethylamino)acetyl]-10,11-dihydro-5h-dibenzo[b,f]azepin-3-yl}carbamate
bdbm50146373
ethyl 5-(2-(dimethylamino)acetyl)-10,11-dihydro-5h-dibenzo[b,f]azepin-3-ylcarbamate
DB13635
Q6586877

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" It was shown that administration of doses in the range of from 3 to 43 mg/kg as well as the repeated use of bonnecor failed to influence the pharmacokinetic parameters."( [The pharmacokinetics and metabolism of bonnecor in rats].
Ioram, U; Klemm, V; Morgenroth, U; Starke, F; Zeriatke, W,
)
0.13
" A significant correlation was revealed between the physicochemical properties, antiarrhythmic activity, pharmacokinetic parameters of bonnecor and its metabolites."( [The relationship between the physicochemical and pharmacokinetic parameters and the anti-arrhythmia activity of bonnecor and its metabolites].
Lyskovtsev, VV; Poppe, H; Rodionov, AP; Zalilov, KIu; Zolotov, NN,
)
0.13
" The pharmacokinetic parameters of bonnecor possess a great variability, the mean values of the parameters are close to the corresponding ones for ethacizine."( [The pharmacodynamics and pharmacokinetics of bonnecor in patients with different disorders of the heart rhythm].
Beloborodov, VL; Kosilova, EE; Lozinskiĭ, LG; Orlov, VA; Tiukavkina, NA; Zalesskaia, MA; Zamotaev, IP; Zeltyn'-Abramov, EM,
)
0.13
"9 ng h mL-1), Cmax (Cmax,ss = 75."( Pharmacokinetics of the antiarrhythmic agent tiracizine: steady state kinetics in comparison with single-dose kinetics.
Berndt, A; Gramatté, T; Oertel, R; Richter, K; Terhaag, B, 1995
)
0.55

Bioavailability

ExcerptReferenceRelevance
" The decrease of bioavailability at oral administration of bonnecor was demonstrated to be related to its intensive conversion in metabolite M-I."( [A comparative study of the pharmacokinetics and pharmacodynamics of bonnecor].
Belinskiaia, GF; Grigor'eva, EK; Ignatova, NA; Lyskovtsev, VV; Rodionov, AP; Sheĭnberg, BV; Tolmacheva, EA,
)
0.13
" The bioavailability was 70%."( [The pharmacokinetics and metabolism of bonnecor in rats].
Ioram, U; Klemm, V; Morgenroth, U; Starke, F; Zeriatke, W,
)
0.13
"Relative bioavailability of a 100 mg tablet formulation of the antiarrhythmic agent tiracizine (CAS 78816-67-8) compared to a 50 mg formulation was assessed in a simple cross over study after single administration of a 100 mg dose to 12 healthy volunteers."( [Relative bioavailability of the antiarrhythmia agent, tiracizine and its metabolites].
Berndt, A; Gramatté, T; Oertel, R; Richter, K; Terhaag, B, 1995
)
0.76
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

ExcerptRelevanceReference
" Proceeding from the comparison of its clinical efficiency and pharmacokinetic parameters in 38 patients, the optimal dosage of the drug was formulated."( [Anti-arrhythmic effect and kinetic parameters of bonnecor in the treatment of extrasystole in patients with acute myocardial infarction].
Beloborodov, VL; Kobeleva, TA; Kosilova, EE; Ol'binskaia, LI; Sizova, ZhM; Tiukavkina, NA, 1990
)
0.28
" The dosage of 15 mg/kg can produce in dogs changes of the hematological and biochemical parameters and cause functional disorders of the cardiac muscle and death of the animals."( [An experimental study of the safety of the preparation bonnecor in trials on dogs].
Batanova, OA; Kovalenko, LP; Liubimov, BI; Popova, GR; Sorokina, AV,
)
0.13
" Considerable accumulation of M1 and M2 was observed during repeated dosing (M1, Cmax,ss = 391."( Pharmacokinetics of the antiarrhythmic agent tiracizine: steady state kinetics in comparison with single-dose kinetics.
Berndt, A; Gramatté, T; Oertel, R; Richter, K; Terhaag, B, 1995
)
0.55
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
dibenzooxazepineAn organic heterotricyclic compound consisting of two benzene rings fused to a seven-membered ring containing one oxygen and one nitrogen atom.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (4)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
TDP1 proteinHomo sapiens (human)Potency40.92400.000811.382244.6684AID686978; AID686979
estrogen nuclear receptor alphaHomo sapiens (human)Potency1.73740.000229.305416,493.5996AID743069
thyroid hormone receptor beta isoform 2Rattus norvegicus (Norway rat)Potency49.50760.000323.4451159.6830AID743065; AID743067
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Nuclear receptor subfamily 1 group I member 3 Homo sapiens (human)IC50 (µMol)4.07800.08001.38974.0780AID1276954
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (6)

Processvia Protein(s)Taxonomy
osteoblast differentiationNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
signal transductionNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
intracellular receptor signaling pathwayNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
positive regulation of transcription by RNA polymerase IINuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
negative regulation of transcription by RNA polymerase IINuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
cell differentiationNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (9)

Processvia Protein(s)Taxonomy
RNA polymerase II transcription regulatory region sequence-specific DNA bindingNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA bindingNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specificNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specificNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
DNA-binding transcription factor activityNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
nuclear receptor activityNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
protein bindingNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
zinc ion bindingNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
sequence-specific double-stranded DNA bindingNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (6)

Processvia Protein(s)Taxonomy
nucleusNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
nucleoplasmNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
cytoplasmNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
cytosolNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
cytoskeletonNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
chromatinNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
nucleusNuclear receptor subfamily 1 group I member 3 Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (5)

Assay IDTitleYearJournalArticle
AID1276954Inverse agonist activity at GST tagged-human CAR-LBD assessed as reduction in fluorescein-PGC1 alpha coactivator recruitment after 1 hr by TR-FRET assay2016European journal of medicinal chemistry, Jan-27, Volume: 108Development of CINPA1 analogs as novel and potent inverse agonists of constitutive androstane receptor.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (49)

TimeframeStudies, This Drug (%)All Drugs %
pre-199020 (40.82)18.7374
1990's25 (51.02)18.2507
2000's0 (0.00)29.6817
2010's2 (4.08)24.3611
2020's2 (4.08)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials9 (13.24%)5.53%
Reviews1 (1.47%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other58 (85.29%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]