Page last updated: 2024-11-06

cicletanine

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

Cicletanine is a synthetic compound that acts as a selective antagonist of the glycine site on the N-methyl-D-aspartate (NMDA) receptor. It was initially developed as a potential treatment for epilepsy, but research showed it had limited efficacy. However, further studies indicated its potential in treating neurological disorders like Alzheimer's disease and Parkinson's disease. Cicletanine's mechanism of action involves blocking the glycine binding site on the NMDA receptor, thus modulating glutamate neurotransmission. Its effects include reducing neuronal hyperexcitability, improving cognitive function, and potentially neuroprotective properties. Despite promising preclinical studies, clinical trials for cicletanine have been limited, and its therapeutic potential remains under investigation. Researchers continue to study cicletanine to better understand its effects on the central nervous system and its potential as a therapeutic agent for neurodegenerative diseases.'

Cross-References

ID SourceID
PubMed CID54910
CHEMBL ID191886
CHEBI ID135078
SCHEMBL ID49794
MeSH IDM0114776

Synonyms (41)

Synonym
justar
bn-50417
bn-1270
tenstaten
win-90000
bn-50418
cicletanine
cycletanide
D03487
89943-82-8
cicletanine (usan/inn)
CHEBI:135078
(+/-)bn-1270
CHEMBL191886
win 90,000
3-(4-chlorophenyl)-6-methyl-1,3-dihydrofuro[3,4-c]pyridin-7-ol
cicletaninum
(+/-)-bn-1270
cicletanina
(+-)-3-(p-chlorophenyl)-1,3-dihydro-6-methylfuro(3,4-c)pyridin-7-ol
chg7qc509w ,
cicletaninum [latin]
cicletanina [spanish]
unii-chg7qc509w
(+-)-bn-1270
cicletanine [usan:inn:ban]
furo(3,4-c)pyridin-7-ol, 3-(4-chlorophenyl)-1,3-dihydro-6-methyl-, (+-)-
cicletanine [mi]
cicletanine [inn]
cicletanine [who-dd]
cicletanine [mart.]
cicletanine [usan]
SCHEMBL49794
AKOS022665941
CVKNDPRBJVBDSS-UHFFFAOYSA-N
(r)-(-)-cicletanine
(+/-)-cicletanine
DB12766
Q5119443
3-(4-chlorophenyl)-6-methyl-1h,3h-furo[3,4-c]pyridin-7-ol
DTXSID70868972

Research Excerpts

Overview

Cicletanine is a racemic furopyridine derivative used as an antihypertensive agent. It stimulates renal and vascular synthesis of prostaglandin (PG) I2 in experimental animals.

ExcerptReferenceRelevance
"Cicletanine is a new antihypertensive drug that stimulates renal and vascular synthesis of prostaglandin (PG) I2 in experimental animals. "( Short-term increase in prostaglandin I2 synthesis caused by cicletanine in patients with essential hypertension.
Imanishi, M; Kimura, G; Kuramochi, M; Matsuoka, H; Omae, T; Tsuji, T; Yasu, T, 1995
)
1.98
"Cicletanine is a new antihypertensive drug that seems to stimulate the synthesis of prostaglandin (PG) I2. "( Effects of cicletanine on prostaglandin I2 and E2 levels in patients with essential hypertension.
Imanishi, M; Yasu, T, 1997
)
2.13
"Cicletanine [(+/-)-C] is a racemic furopyridine derivative used as an antihypertensive agent. "( Stereoselective biotransformation of cicletanine in cultured rat and human hepatocytes.
Lamiable, D; Menard, C; Morin, E; Ratanasavanh, D; Vistelle, R, 2000
)
2.02
"Cicletanine is an antihypertensive/vasorelaxant/natriuretic agent of unknown mechanism. "( Inhibition of low Km cyclic GMP phosphodiesterases and potentiation of guanylate cyclase activators by cicletanine.
Buchholz, A; Dundore, RL; Harris, AL; Pagani, ED; Silver, PJ, 1990
)
1.94
"Cicletanine (CIC) is a novel antihypertensive agent."( Cicletanine modulates endothelin-induced renal vasoconstriction in the rat.
Braquet, P; Cornet, S; Pirotzky, E; Teillot, M, 1991
)
2.45
"Cicletanine is a new antihypertensive agent. "( [Effect of cicletanine on a sudden death model in dogs].
Braquet, P; Guillon, JM; Thievant, P, 1989
)
2.11
"Cicletanine is a new antihypertensive agent known for being able to stimulate prostaglandin synthesis in vivo and in endothelial cell cultures. "( [Effects of treatment with cicletanine on kidney PGE2 and PGI1 in spontaneously hypertensive rats].
Bakri, F; Berthet, P; Bosquet, D; Deby, C; Deby-Dupont, G; Droy-Lefaix, MT, 1989
)
2.02
"Cicletanine is a new antihypertensive molecule which acts directly on vascular smooth muscle by increasing prostacyclin synthesis and interacting with various agents which mobilize intracellular Ca2+ ions. "( General pharmacology of cicletanine.
Clostre, F; Etienne, A, 1988
)
2.02

Effects

ExcerptReferenceRelevance
"Cicletanine has a pharmacokinetic profile well fitted to the therapy of this age group."( [Efficacy and tolerability of cycletanine in aged patients with hypertension].
Bodak, A; Forette, F; Gavardin, T; Jungers, P; Metellus, J; Salom, M; Tarrade, T,
)
0.85
"Cicletanine has a pharmacokinetic profile well fitted to the therapy of this age group."( [Efficacy and tolerability of cycletanine in aged patients with hypertension].
Bodak, A; Forette, F; Gavardin, T; Jungers, P; Metellus, J; Salom, M; Tarrade, T,
)
0.85

Actions

Cicletanine led to an increase in eNOS phosphorylation, cytochrome c reductase activity, L-arginine conversion to L-citrulline, as well as NO production. CicleTanine did not inhibit contraction induced by Ca2+ in the permeabilized rabbit mesenteric artery with alpha-toxin.

ExcerptReferenceRelevance
"Cicletanine led to an increase in eNOS (Ser¹¹⁷⁷) phosphorylation, cytochrome c reductase activity, L-arginine conversion to L-citrulline, as well as NO production."( Cicletanine stimulates eNOS phosphorylation and NO production via Akt and MAP kinase/Erk signaling in sinusoidal endothelial cells.
Liu, S; Rockey, DC, 2013
)
2.55
"Cicletanine did not inhibit contraction induced by Ca2+ in the permeabilized rabbit mesenteric artery with alpha-toxin."( Cicletanine-induced decreases in cytosolic Ca2+ level and contraction in vascular smooth muscle.
Izumi, M; Karaki, H; Mitsui-Saito, M; Ozaki, H, 1998
)
2.46
"(-)-Cicletanine displays greater vasorelaxant activity v (+)-enantiomer."( Vasorelaxant effects of cicletanine and its (+)- and (-)-enantiomers in isolated human pulmonary arteries.
Bagrov, AY; Dmitrieva, RI; Droy-Lefaix, MT, 1998
)
1.09
"3. Cicletanine and ajoene cause a concentration-dependent membrane hyperpolarization and are potent vasodilators."( Potassium channel activation in vascular smooth muscle.
Emden, J; Mironneau, J; Siegel, G; Stock, G; Wenzel, K, 1992
)
0.8

Treatment

Cicletanine treatment significantly decreased the incidence of ventricular arrhythmias, increased cardiac cGMP and nitric oxide content and reduced cardiac cAMP level. The drug did not affect plasma concentration of total cholesterol or triglyceride or free fatty acid.

ExcerptReferenceRelevance
"Cicletanine treatment significantly decreased the incidence of ventricular arrhythmias, increased cardiac cGMP and nitric oxide content and reduced cardiac cAMP level. "( Beneficial cardiac effects of cicletanine in conscious rabbits with metabolic syndrome.
Drimba, L; Hegedüs, C; Németh, J; Peitl, B; Sári, R; Szilvássy, Z; Yin, D, 2012
)
2.11
"Cicletanine-treated rats exhibited a 56-mm Hg reduction in blood pressure (P<0.01) and a 30% reduction in left ventricular weight, whereas cardiac alpha-1 Na/K-ATPase protein and MBG levels were unchanged."( Myocardial PKC beta2 and the sensitivity of Na/K-ATPase to marinobufagenin are reduced by cicletanine in Dahl hypertension.
Agalakova, NI; Bagrov, AY; Droy-Lefaix, MT; Fedorova, OV; Lakatta, EG; Talan, MI, 2003
)
1.26
"Cicletanine treatment did not affect plasma concentration of total cholesterol or triglyceride or free fatty acid; in contrast, it significantly decreased low-density lipoprotein (LDL) cholesterol and increased high-density lipoprotein (HDL) cholesterol."( Lipid metabolism and renal protection by chronic cicletanine treatment in Dahl salt-sensitive rats with salt-induced hypertension.
Akie, Y; Funahashi, N; Goto, A; Hirawa, N; Ichikawa, A; Kawabata, Y; Omata, M; Uehara, Y, 1997
)
1.27
"Cicletanine treatment (500 mg of cicletanine/kg of chow) for 6 weeks lowered blood pressure by 19% in Dahl S rats challenged with a high-salt (4%) diet."( Evidence for medial-mass regression in the vascular wall of Dahl hypertensive rats by cicletanine treatment.
Iwai, J; Kawabata, Y; Matsuoka, H; Nagata, T; Numabe, A; Sugimoto, T; Takabatake, Y; Uehara, Y; Yagi, S, 1991
)
1.23

Pharmacokinetics

Cicletanine is the first derivative of a new class of antihypertensive drugs, the furopyridines.

ExcerptReferenceRelevance
"A pharmacokinetic study of cicletanine, a new class of antihypertensive drugs was performed in ten healthy volunteers after administration of 50 mg single oral dose."( Pharmacokinetic study of cicletanine in healthy volunteers.
Obach, R; Peraire, C; Pruñonosa, J; Torrent, J, 1992
)
0.88
" A pharmacokinetic study was performed in 8 non-patient subjects who were given 50 mg oral daily doses for 7 days."( Multiple dose pharmacokinetic study of cicletanine in healthy volunteers.
Azcona, O; Nomen, M; Obach, R; Peraire, C; Pruñonosa, J; Torrent, J, 1991
)
0.55
" In normotensive subjects with normal renal function, cicletanine was rapidly and regularly absorbed, its apparent elimination half-life established around 7 h, and both its renal clearance (0."( Influence of renal insufficiency on the pharmacokinetics of cicletanine and its effects on the urinary excretion of electrolytes and prostanoids.
Benzoni, D; Cuisinaud, G; Ferry, N; Geoffroy, J; Pozet, N; Sassard, J; Zech, PY, 1988
)
0.77
"Results of the different pharmacokinetic studies performed with cicletanine, the first derivative of a new class of antihypertensive drugs, the furopyridines, are reviewed in this article."( Clinical pharmacokinetics of cicletanine hydrochloride.
Fredj, G, 1988
)
0.8
"73 m2 or treated by chronic haemodialysis) with a significant increase in elimination half-life and tissue accumulation of the drug."( Pharmacokinetics of cicletanine in patients with impaired renal function.
Jungers, P, 1988
)
0.6

Dosage Studied

Hydrochlorothiazide and cicletanine were weak calcium antagonists. They shifted the calcium dose-response curve half a log unit to the right. A cicle tanine concentration attained by the dosage given to patients is sufficient to produce effects.

ExcerptRelevanceReference
" A cicletanine concentration, which is attained by the dosage given to patients, is sufficient to produce these effects."( Potassium channel activation in vascular smooth muscle.
Emden, J; Mironneau, J; Siegel, G; Stock, G; Wenzel, K, 1992
)
0.9
" A cicletanine concentration, which is attained by the dosage given to patients, is sufficient to produce these effects."( Potassium channel activation, hyperpolarization, and vascular relaxation.
Buddecke, E; Loirand, G; Schmidt, A; Schnalke, F; Siegel, G; Stock, G; Walter, A, 1991
)
0.9
" In this study, the effects of cicletanine at two dosage levels (3."( [Comparison of the effects of cicletanine and captopril on kidney and heart lesions in spontaneously hypertensive rats (SHR-SP)].
Bakri, F; Bosquet, D; Droy, MT; Guillemain, J; Lhuintre, Y; Ruchoux, MM, 1989
)
0.85
" The initial dosage (50 mg/day) was doubled in only one-third of the patients."( [Antihypertensive effectiveness and tolerance of cicletanine. Results obtained with monotherapy in a large population].
Allard, M; Berthet, P; Bosquet, D; Paillasseur, JL; Tarrade, T, 1989
)
0.53
" There was a dose-response effect such that in double-blind studies of 1 month's duration, 50 mg/d was the minimum effective dose in mild to moderate hypertensive patients, while a higher dose, 200 mg/d, was more effective in patients with severe hypertension."( Determination of the optimal dose of the antihypertensive drug cicletanine hydrochloride in man.
Guinot, P; Jewitt-Harris, J; Tarrade, T, 1989
)
0.52
" Analysis of the responder rate indicated a significant dose-response relationship which was clinically relevant only for the 50 and 100 mg doses."( Review of three studies to determine the efficacy and tolerance of cicletanine in the short- and long-term treatment of essential hypertension.
Fodor, GP; Guinot, P, 1988
)
0.51
" In mild to moderate hypertension, the dose-response relationship observed after one month of treatment on diastolic (DBP) and systolic (SBP) blood pressure disappeared during the third month."( Efficacy and tolerance of cicletanine, a new antihypertensive agent: overview of 1226 treated patients.
Guinot, P; Tarrade, T, 1988
)
0.58
" Hydrochlorothiazide (10 microM) and cicletanine (10 microM) were weak calcium antagonists shifting the calcium dose-response curve half a log unit to the right."( Ion channel involvement in the acute vascular effects of thiazide diuretics and related compounds.
Calder, JA; Schachter, M; Sever, PS, 1993
)
0.56
" Cumulative urine samples were collected predosing and over 24 h after dosing in each period to compare urine electrolyte excretion profiles of potassium (UKV), sodium (UNaV), magnesium, calcium, phosphate, chloride, and pH among groups."( A comparison of the natriuretic and kaliuretic effects of cicletanine and hydrochlorothiazide in prehypertensive and hypertensive humans.
Beals, C; Carey, RM; De Lepeleire, I; Fernandez, R; Gildea, J; Greenwalt, DM; Johnson-Levonas, AO; Malice, MP; McGrath, HE; Mitta, S; Nunes, I; Sisk, CM; Van Dyck, K; Wagner, F; Wiegert, E, 2012
)
0.62
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
organochlorine compoundAn organochlorine compound is a compound containing at least one carbon-chlorine bond.
[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]

Bioassays (1)

Assay IDTitleYearJournalArticle
AID237685Lipophilicity determined as logarithm of the partition coefficient in the alkane/water system2005Journal of medicinal chemistry, May-05, Volume: 48, Issue:9
Calculating virtual log P in the alkane/water system (log P(N)(alk)) and its derived parameters deltalog P(N)(oct-alk) and log D(pH)(alk).
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (188)

TimeframeStudies, This Drug (%)All Drugs %
pre-199077 (40.96)18.7374
1990's92 (48.94)18.2507
2000's13 (6.91)29.6817
2010's6 (3.19)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 41.26

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 strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index41.26 (24.57)
Research Supply Index5.39 (2.92)
Research Growth Index4.26 (4.65)
Search Engine Demand Index61.82 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (41.26)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials23 (11.73%)5.53%
Reviews6 (3.06%)6.00%
Case Studies3 (1.53%)4.05%
Observational0 (0.00%)0.25%
Other164 (83.67%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (2)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-ranging Study of Cicletanine in Subjects With Pulmonary Arterial Hypertension [NCT00832507]Phase 2162 participants (Actual)Interventional2009-01-31Terminated
Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium [NCT02709031]Phase 1/Phase 224 participants (Anticipated)Interventional2022-06-30Not yet recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]