Compounds > lesogaberan
Page last updated: 2024-11-11

lesogaberan

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

Description

lesogaberan: a gastrointestinal system agent; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9833984
CHEMBL ID448343
SCHEMBL ID349234
MeSH IDM0541150

Synonyms (27)

Synonym
[(2r)-3-amino-2-fluoropropyl]phosphinic acid
azd3355
bdbm24195
3-aminopropylphosphinic derivative, (r)-7
CHEMBL448343
azd-3355
lesogaberan
344413-67-8
4d6q6hgc7z ,
unii-4d6q6hgc7z
lesogaberan [inn]
(2r)-3-amino-2-fluoropropylphosphinic acid
AKOS006338534
lesogaberan [who-dd]
gtpl7705
SCHEMBL349234
LJNUIEQATDYXJH-GSVOUGTGSA-N
(2r)-(3-amino-2-fluoropropyl)phosphinic acid
DTXSID20188011
(r)-(3-amino-2-fluoropropyl) phosphinic acid
DB11920
Q4864584
HY-10061
CS-0002426
A902100
((r)-3-amino-2-fluoropropyl)phosphinic acid
[(2r)-3-amino-2-fluoropropyl]-hydroxy-oxophosphanium

Research Excerpts

Overview

Lesogaberan (AZD3355) is a novel reflux inhibitor developed as an add-on treatment to proton pump inhibitors (PPIs) for symptom relief in patients with gastroesophageal reflux disease who have a partial response to PPI therapy.

ExcerptReferenceRelevance
"Lesogaberan (AZD3355) is a peripherally restricted GABAB receptor agonist with limited central nervous system activity that inhibits transient LES relaxation in dogs."( The novel, peripherally restricted GABAB receptor agonist lesogaberan (AZD3355) inhibits acid reflux and reduces esophageal acid exposure as measured with 24-h pHmetry in dogs.
Brändén, L; Fredriksson, A; Harring, E; Jensen, J; Lehmann, A, 2010)		1.33
"Lesogaberan (AZD3355) is a novel reflux inhibitor developed as an add-on treatment to proton pump inhibitors (PPIs) for symptom relief in patients with gastroesophageal reflux disease who have a partial response to PPI therapy."( Pharmacokinetic profile of lesogaberan (AZD3355) in healthy subjects: a novel GABA(B)-receptor agonist reflux inhibitor.
Holmberg, AA; Niazi, M; Ruth, M; Skrtic, S, 2011)		2.11
"Lesogaberan is a potent gamma amino butyric acid agonist and has been evaluated for its utility in treatment of gastroesophageal reflux disease. "( Early pharmaceutical evaluation of a crystalline and hygroscopic GABAB receptor agonist.
Andersson, T; Berntsson, V; Sigfridsson, K; Wang, Y, 2013)		1.83
"Lesogaberan (AZD3355) is a novel γ-aminobutyric acid B-type receptor agonist designed to treat gastro-oesophageal reflux disease (GERD) by inhibiting transient lower oesophageal sphincter relaxations. "( Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial.
Björck, K; Denison, H; Karlsson, M; Shaheen, NJ; Silberg, DG, 2013)		2.14

Treatment

ExcerptReferenceRelevance
"Treatment with lesogaberan, compared with placebo, resulted in a significantly larger proportion of responders to treatment (16% vs 8% of patients; p=0.026) and cumulative proportion of responders over time (log-rank p=0.0195)."( A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial.
Beaumont, H; Björck, K; Boeckxstaens, GE; Denison, H; Hatlebakk, JG; Karlsson, M; Silberg, DG, 2011)		1.01

Toxicity

ExcerptReferenceRelevance
" Nevertheless, it is an example of successful formulation development designed to minimize the occurrence of a compound's adverse effect while retaining its pharmacodynamic action."( Reducing Adverse Effects During Drug Development: The Example of Lesogaberan and Paresthesia.
Aurell-Holmberg, A; Denison, H; Jensen, JM; Lehmann, A; Ruth, M; Rydholm, H; Söderlind, E; von Corswant, C, 2016)		0.67

Pharmacokinetics

Lesogaberan is being developed as an add-on treatment for the management of patients with GERD who have a partial response to proton pump inhibitor (PPI) therapy. There was no observed pharmacokinetic interaction when concomitantly administered to healthy subjects.

ExcerptReferenceRelevance
" As lesogaberan is being developed as an add-on treatment for the management of patients with GERD who have a partial response to proton pump inhibitor (PPI) therapy, it is important to rule out any clinically important pharmacokinetic drug-drug interaction between lesogaberan and PPIs."( Evaluation of the pharmacokinetic interaction between lesogaberan (AZD3355) and esomeprazole in healthy subjects.
Holmberg, AA; Miller, F; Niazi, M; Ruth, M; Silberg, DG, 2010)		1.17
"The presence or absence of pharmacokinetic interactions between lesogaberan and esomeprazole was assessed by measuring the steady-state area under the plasma concentration-time curves during the dosing interval (AUC(τ)) and the maximum observed plasma concentration (C(max)) for lesogaberan and esomeprazole."( Evaluation of the pharmacokinetic interaction between lesogaberan (AZD3355) and esomeprazole in healthy subjects.
Holmberg, AA; Miller, F; Niazi, M; Ruth, M; Silberg, DG, 2010)		0.85
"There was no observed pharmacokinetic interaction between lesogaberan and esomeprazole when concomitantly administered to healthy subjects, and concomitant therapy was well tolerated."( Evaluation of the pharmacokinetic interaction between lesogaberan (AZD3355) and esomeprazole in healthy subjects.
Holmberg, AA; Miller, F; Niazi, M; Ruth, M; Silberg, DG, 2010)		0.85
"The aim of this study was to evaluate the pharmacokinetic profile of lesogaberan in healthy subjects after single oral and intravenous administration of (14)C-labeled lesogaberan and non-(14)C-labeled lesogaberan."( Pharmacokinetic profile of lesogaberan (AZD3355) in healthy subjects: a novel GABA(B)-receptor agonist reflux inhibitor.
Holmberg, AA; Niazi, M; Ruth, M; Skrtic, S, 2011)		0.9
" The terminal half-life of lesogaberan was between 11 and 13 hours."( Pharmacokinetic profile of lesogaberan (AZD3355) in healthy subjects: a novel GABA(B)-receptor agonist reflux inhibitor.
Holmberg, AA; Niazi, M; Ruth, M; Skrtic, S, 2011)		0.96

Bioavailability

lesogaberan is rapidly absorbed with high bioavailability. Most of the dose is excreted by the kidneys either as the parent compound or as metabolites. The effect of food on the bioavailability of this compound has not been assessed.

ExcerptReferenceRelevance
"Orally administered lesogaberan is rapidly absorbed with high bioavailability and the majority of the dose is excreted by the kidneys either as the parent compound or as metabolites."( Pharmacokinetic profile of lesogaberan (AZD3355) in healthy subjects: a novel GABA(B)-receptor agonist reflux inhibitor.
Holmberg, AA; Niazi, M; Ruth, M; Skrtic, S, 2011)		0.99
"The novel Type B gamma-aminobutyric acid (GABAB)-receptor agonist lesogaberan (AZD3355) has been evaluated as an add-on to proton pump inhibitor treatment for gastroesophageal reflux disease, but the effect of food on the bioavailability of this compound has not been assessed."( Effect of food on the bioavailability of lesogaberan given as an oral solution or as modified-release capsules in healthy male volunteers.
Fransson, B; Holmberg, AA; Miller, F; Niazi, M; Ruth, M; Silberg, DG, 2012)		0.88
" These findings suggest that the initial rate of absorption plays an important part in the development of paresthesia."( Reducing Adverse Effects During Drug Development: The Example of Lesogaberan and Paresthesia.
Aurell-Holmberg, A; Denison, H; Jensen, JM; Lehmann, A; Ruth, M; Rydholm, H; Söderlind, E; von Corswant, C, 2016)		0.67

Dosage Studied

The presence or absence of pharmacokinetic interactions between lesogaberan and esomeprazole was assessed by measuring the steady-state area under the plasma concentration-time curves during the dosing interval. Plasma samples were taken at 2 and 24 h after dosing.

ExcerptRelevanceReference
" AZD3355 potently stimulated recombinant human GABA(B) receptors and inhibited TLESR in dogs, with a biphasic dose-response curve."( (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action.
Antonsson, M; Blackshaw, LA; Brändén, L; Bräuner-Osborne, H; Christiansen, B; Dent, J; Elebring, T; Holmberg, AA; Jacobson, BM; Jensen, J; Lehmann, A; Mattsson, JP; Nilsson, K; Oja, SS; Page, AJ; Saransaari, P; von Unge, S, 2009)		0.35
"The presence or absence of pharmacokinetic interactions between lesogaberan and esomeprazole was assessed by measuring the steady-state area under the plasma concentration-time curves during the dosing interval (AUC(τ)) and the maximum observed plasma concentration (C(max)) for lesogaberan and esomeprazole."( Evaluation of the pharmacokinetic interaction between lesogaberan (AZD3355) and esomeprazole in healthy subjects.
Holmberg, AA; Miller, F; Niazi, M; Ruth, M; Silberg, DG, 2010)		0.85
"Volunteers were randomized to receive a single dose of either orally dosed (100 mg) or intravenously infused (20 mg) non-(14)C-labeled lesogaberan, and then orally (100 mg) or intravenously (20 mg) administered (14)C-labeled lesogaberan in a crossover design."( Pharmacokinetic profile of lesogaberan (AZD3355) in healthy subjects: a novel GABA(B)-receptor agonist reflux inhibitor.
Holmberg, AA; Niazi, M; Ruth, M; Skrtic, S, 2011)		0.87
" Urine was collected from three male Wistar rats for 24 h after dosing with (14)C-labelled lesogaberan (170 mg/kg, 10 MBq/kg); plasma samples were taken 2 and 24 h after dosing."( Identification of the metabolites of lesogaberan using linear trap quadrupole orbitrap mass spectrometry and hydrophilic interaction liquid chromatography.
Aurell-Holmberg, A; Castagnoli, N; Ekdahl, A, 2013)		0.88
" Plasma samples were taken at various time points after lesogaberan dosing in two clinical and three preclinical studies."( Systemic exposure to the metabolites of lesogaberan in humans and animals: a case study of metabolites in safety testing.
Ekdahl, A; Holmberg, AA; Weidolf, L, 2014)		0.92
" This study aimed to explore the dose-response effect of lesogaberan on reflux episodes in partial responders."( Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study.
Miller, F; Miner, PB; Pandolfino, J; Ruth, M; Silberg, DG, 2014)		0.95
" A high prevalence of paresthesia was observed in healthy individuals after dosing with lesogaberan in early-phase clinical trials."( Reducing Adverse Effects During Drug Development: The Example of Lesogaberan and Paresthesia.
Aurell-Holmberg, A; Denison, H; Jensen, JM; Lehmann, A; Ruth, M; Rydholm, H; Söderlind, E; von Corswant, C, 2016)		0.89
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gamma-aminobutyric acid type B receptor subunit 2Rattus norvegicus (Norway rat)Ki0.00510.00510.06830.2200AID1798404
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (5)

Assay IDTitleYearJournalArticle
AID626682Agonist activity against human GABAB receptor expressed in HEK cells assessed as increase in cytoplasmic calcium level2011Bioorganic & medicinal chemistry letters, Nov-01, Volume: 21, Issue:21
Discovery of a novel potent GABA(B) receptor agonist.
AID339809Agonist activity at human recombinant GABABreceptor expressed in CHO-K1 cells assessed as inhibition of intracellular calcium release by FLIPR2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Synthesis and pharmacological evaluation of novel gamma-aminobutyric acid type B (GABAB) receptor agonists as gastroesophageal reflux inhibitors.
AID339810Intrinsic activity at human recombinant GABAB receptor expressed in CHO-K1 cells assessed as inhibition of intracellular calcium release by FLIPR relative to GABA2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Synthesis and pharmacological evaluation of novel gamma-aminobutyric acid type B (GABAB) receptor agonists as gastroesophageal reflux inhibitors.
AID339808Displacement of [3H]GABA from GABABreceptor in rat brain synaptic membranes2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Synthesis and pharmacological evaluation of novel gamma-aminobutyric acid type B (GABAB) receptor agonists as gastroesophageal reflux inhibitors.
AID1798404[3H]GABA Filtration Binding Assay (Ki) and FLIPR Assay for Agonism (EC50) from Article 10.1021/jm701425k: \\Synthesis and pharmacological evaluation of novel gamma-aminobutyric acid type B (GABAB) receptor agonists as gastroesophageal reflux inhibitors.\\2008Journal of medicinal chemistry, Jul-24, Volume: 51, Issue:14
Synthesis and pharmacological evaluation of novel gamma-aminobutyric acid type B (GABAB) receptor agonists as gastroesophageal reflux inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (28)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's3 (10.71)29.6817
2010's24 (85.71)24.3611
2020's1 (3.57)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 25.79

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 Index25.79 (24.57)
Research Supply Index3.64 (2.92)
Research Growth Index4.75 (4.65)
Search Engine Demand Index29.35 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (25.79)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials9 (32.14%)5.53%
Reviews5 (17.86%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other14 (50.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (10)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Double-blind, Placebo Controlled, Randomized, Two Centre Phase IIA Pharmacodynamic Cross-over Study to Assess the Effect of AZD3355, 65 mg Bid, on Transient Lower Esophageal Sphincter Relaxations (TLESRs) in GERD Patients With an Incomplete Response to [NCT00743444]Phase 227 participants (Actual)Interventional2007-02-28Completed
[NCT01005251]Phase 2661 participants (Actual)Interventional2009-10-31Completed
A Phase I, Open Label, Non-randomized, Parallel Group, Pharmacokinetic Study in Subjects With Normal Renal Function, Moderate or Severe Renal Impairment Receiving a Single Dose of Oral 130 mg AZD3355 [NCT00863161]Phase 123 participants (Actual)Interventional2009-03-31Completed
A Double-blind, Randomized, Cross-over Design, Phase 1 Pharmacodynamic Study to Investigate the Effect of Different Formulations of AZD3355 for the Development of Paresthesiae After Dosing in Healthy Subjects [NCT00688402]Phase 148 participants (Anticipated)Interventional2008-04-30Completed
An Open, Randomised, Three Period Cross, Single Centre, Phase 1 Pharmacokinetic Interaction Study of the Reflux Inhibitor AZD3355 150 mg Bid and Esomeprazole 40 mg od After 7 Days of Treatment in Healthy Volunteers [NCT00684190]Phase 130 participants (Actual)Interventional2008-03-31Completed
A Randomized, Double-blind, Placebo Controlled, Phase IIA Study to Assess the Effect on Gastroesophageal Reflux Disease (GERD) Symptoms, Pharmacokinetics, Safety and Tolerability of 4 Weeks Treatment With AZD3355 65 mg Bid as add-on Treatment to a Proton [NCT00394472]Phase 2244 participants (Actual)Interventional2006-11-30Completed
A Phase 1 Single Centre Single-blind Randomised Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral AZD3355 After Administration of Single Ascending Doses and Multiple Repeated Doses in Healthy Male Volunteers [NCT00757419]Phase 154 participants (Anticipated)Interventional2008-09-30Completed
Validation of Patient-reported Outcomes Measures for the Assessment of GERD Symptoms and Their Subsequent Impact on Patients With Partial Response to Proton Pump Inhibitor (PPI) Treatment in a Two Part Multi-center Phase IIa Study Including a Four Week Ra [NCT00703534]Phase 2478 participants (Actual)Interventional2008-05-31Completed
Efficacy and Safety of Lesogaberan (AZD3355) in Chinese Patients With Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy: a Randomized Placebo-controlled Trial [NCT02818309]Phase 272 participants (Anticipated)Interventional2015-01-31Active, not recruiting
A Double-blind, Placebo Controlled, Randomised, Phase IIA Pharmacodynamic 4-way Cross-over Study to Estimate the Dose Response Relationship of AZD3355 on the Number of Reflux Episodes Assessed by Impedance/pH in Patients With GERD and a Partial Response t [NCT01043185]Phase 227 participants (Actual)Interventional2009-12-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00394472 (2) [back to overview]Number of Participants With at Most One Day With Not More Than Mild Intensity of the Symptoms 'a Burning Feeling Behind the Breastbone' and 'Unpleasant Movement of Material Upwards From the Stomach' During the Last Seven Days of Treatment
NCT00394472 (2) [back to overview]Plasma Concentration (µmol/L) of AZD3355 Analysed From Blood Sample Taken in the Interval One to Two Hours After the First Intake of AZD3355 65 mg Capsule
NCT00743444 (3) [back to overview]Area Under the Plasma Concentration vs. Time Curve (AUCtau) During 0-12 Hours Post First Dose Calculated by the Log/Linear Trapezoidal Method.
NCT00743444 (3) [back to overview]Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs) 0-3 Hours Post Meal, Post Third Dose
NCT00743444 (3) [back to overview]Total Number Reflux Episodes 0-24 Hours Post First Dose
NCT01005251 (2) [back to overview]Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms.
NCT01005251 (2) [back to overview]Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation)
NCT01043185 (4) [back to overview]Number of Acid Reflux Episodes
NCT01043185 (4) [back to overview]Number of Weakly Acidic Reflux Episodes
NCT01043185 (4) [back to overview]Number of Weakly Alkaline Reflux Episodes
NCT01043185 (4) [back to overview]Total Number of Reflux Episodes During 24 Hours

Number of Participants With at Most One Day With Not More Than Mild Intensity of the Symptoms 'a Burning Feeling Behind the Breastbone' and 'Unpleasant Movement of Material Upwards From the Stomach' During the Last Seven Days of Treatment

Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Disease Questionnaire (RDQ) diary (NCT00394472)
Timeframe: Twice daily during the last seven days on treatment

InterventionParticipants (Number)
AZD335517
Placebo8

[back to top]

Plasma Concentration (µmol/L) of AZD3355 Analysed From Blood Sample Taken in the Interval One to Two Hours After the First Intake of AZD3355 65 mg Capsule

(NCT00394472)
Timeframe: An interval of one to two hours after the first intake of AZD3355 65 mg capsule

Interventionμmol/L (Mean)
AZD33550.96

[back to top]

Area Under the Plasma Concentration vs. Time Curve (AUCtau) During 0-12 Hours Post First Dose Calculated by the Log/Linear Trapezoidal Method.

The AUCtau was calculated for each patient in the period with AZD3355 treatment by the Log-Linear Trapezoidal Method. The descriptive geometric mean of the individual AUCtau values is reported here. (NCT00743444)
Timeframe: 0-12 hours post first dose

Interventionμmol*hours / L (Geometric Mean)
AZD33557.16

[back to top]

Number of Transient Lower Esophageal Sphincter Relaxations (TLESRs) 0-3 Hours Post Meal, Post Third Dose

"The number of relaxations for each patient in each period was determined from manometric tracings according to previously published criteria (R.H. Holloway, R. Penagini and A.C. Ireland, Criteria for objective definition of transient lower esophageal sphincter relaxation, Am J Physiol 268 (1995), pp. G128-G133).~The analysis of the number of TLESRs was based on an analysis of variance (ANOVA) for log-transformed data. The 95% level confidence interval (CI) limits were transformed back to the original scale to give CIs for the geometric mean for each treatment." (NCT00743444)
Timeframe: 0-3 hours post meal, post third dose

InterventionRelaxations (Geometric Mean)
AZD335511.6
Placebo15.5

[back to top]

Total Number Reflux Episodes 0-24 Hours Post First Dose

Number of reflux episodes assessed during the 24-hour ambulatory impedance-pH recording. (NCT00743444)
Timeframe: 0-24 hours

InterventionEpisodes (Geometric Mean)
AZD335530.6
Placebo50.5

[back to top]

Absolute Change From Baseline to Treatment Period in Percent Days With at Most Mild GERD Symptoms.

"Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Symptom Questionnaire diary~(GERD = Gastroesophageal Reflux Disease)" (NCT01005251)
Timeframe: The 7 days before randomisation (baseline) and during 26-30 days of treatment

InterventionPercent (Median)
AZD3355 60 mg10.7
AZD3355 120 mg17.2
AZD3355 180 mg11.9
AZD3355 240 mg12.5
Placebo0

[back to top]

Number of Participants With a Change in GERD Symptoms Corresponding to at Least Three More Days of Not More Than Mild Symptoms on Average Per Week During Treatment (Approximately 4 Weeks) Than During Baseline (the 7 Days Before Randomisation)

"Symptom intensity rated by participants twice daily on a six-graded Likert scale (Did not have; Very mild; Mild; Moderate; Moderately severe; Severe) using an electronic Reflux Symptom Questionnaire diary.~(GERD = Gastroesophageal Reflux Disease)" (NCT01005251)
Timeframe: The 7 days before randomisation (baseline) and during 26-30 days of treatment

InterventionParticipants (Number)
AZD3355 60 mg28
AZD3355 120 mg32
AZD3355 180 mg32
AZD3355 240 mg33
Placebo25

[back to top]

Number of Acid Reflux Episodes

Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH <4 (or a drop of at least 1 pH unit if pH is already <4) lasting more than 5 s. (NCT01043185)
Timeframe: Measured during 24 hours at 4 different visits with a 7-28 days interval between

InterventionEpisodes (Geometric Mean)
AZD3355 30 mg9.6
AZD3355 90 mg8.0
AZD3355 120 mg6.2
AZD3355 240 mg6.3
Placebo14.7

[back to top]

Number of Weakly Acidic Reflux Episodes

Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH 4.0-6.5 lasting more than 5 s. (NCT01043185)
Timeframe: Measured during 24 hours at 4 different visits with a 7-28 days interval between

InterventionEpisodes (Geometric Mean)
AZD3355 30 mg37.0
AZD3355 90 mg35.4
AZD3355 120 mg28.7
AZD3355 240 mg28.4
Placebo51.6

[back to top]

Number of Weakly Alkaline Reflux Episodes

Number of reflux episodes as defined for the primary outcome measure with an intraesophageal pH ≥6.5 lasting more than 5 s. (NCT01043185)
Timeframe: Measured during 24 hours at 4 different visits with a 7-28 days interval between

InterventionEpisodes (Median)
AZD3355 30 mg0
AZD3355 90 mg0
AZD3355 120 mg0
AZD3355 240 mg0
Placebo0

[back to top]

Total Number of Reflux Episodes During 24 Hours

Number of reflux episodes assessed during ambulatory impedance-pH recording (defined as starting with a drop in impedance to below 50% of baseline and ending when impedance recovers to above 50% of baseline) (NCT01043185)
Timeframe: Measured during 24 hours at 4 different visits with a 7-28 days interval between

InterventionEpisodes (Geometric Mean)
AZD3355 30 mg59.4
AZD3355 90 mg50.7
AZD3355 120 mg44.3
AZD3355 240 mg38.0
Placebo80.5

[back to top]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
gamma-aminobutyric acid
gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.. gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4.		2.0810amino acid zwitterion;
gamma-amino acid;
monocarboxylic acid		human metabolite;
neurotransmitter;
Saccharomyces cerevisiae metabolite;
signalling molecule
baclofen
[no description available]		7.9291amino acid zwitterion;
gamma-amino acid;
monocarboxylic acid;
monochlorobenzenes;
primary amino compound		central nervous system depressant;
GABA agonist;
muscle relaxant
sk&f 97541
3-aminopropyl(methyl)phosphinic acid: structure given in first source; GABA-A receptor antagonist		2.4620
isoxazoles
Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.. isoxazole : A monocyclic heteroarene with a structure consisting of a 5-membered ring containing three carbon atoms and an oxygen and nitrogen atom adjacent to each other. It is the parent of the class of isoxazoles.. isoxazoles : Oxazoles in which the N and O atoms are adjacent.		4.1410isoxazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
erythromycin
Erythromycin: A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.. erythromycin : Any of several wide-spectrum macrolide antibiotics obtained from actinomycete Saccharopolyspora erythraea (formerly known as Streptomyces erythraeus).. erythromycin A : An erythromycin that consists of erythronolide A having 2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribo-hexopyranosyl and 3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl residues attahced at positions 4 and 6 respectively.		2.0510cyclic ketone;
erythromycin
dronabinol
Dronabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.. Delta(9)-tetrahydrocannabinol : A diterpenoid that is 6a,7,8,10a-tetrahydro-6H-benzo[c]chromene substituted at position 1 by a hydroxy group, positions 6, 6 and 9 by methyl groups and at position 3 by a pentyl group. The principal psychoactive constituent of the cannabis plant, it is used for treatment of anorexia associated with AIDS as well as nausea and vomiting associated with cancer chemotherapy.		2.0510benzochromene;
diterpenoid;
phytocannabinoid;
polyketide		cannabinoid receptor agonist;
epitope;
hallucinogen;
metabolite;
non-narcotic analgesic
Arbaclofen
[no description available]		2.0610organonitrogen compound;
organooxygen compound
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		4.14101,2,3-triazole
6-methyl-2-(phenylethynyl)pyridine
6-methyl-2-(phenylethynyl)pyridine: an mGlu5 antagonist. 2-methyl-6-(phenylethynyl)pyridine : A methylpyridine that coinsists of 2-methylp[yridine bearing an additional phenylethynyl group at position 6. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw.		2.0510acetylenic compound;
methylpyridines		anxiolytic drug;
metabotropic glutamate receptor antagonist
3-aminopropylphosphinic acid
3-aminopropylphosphinic acid: structure given in first source; selective GABA receptor agonist		2.4620
s 1743
Esomeprazole: The S-isomer of omeprazole.. esomeprazole : A 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole that has S configuration at the sulfur atom. An inhibitor of gastric acid secretion, it is used (generally as its sodium or magnesium salt) for the treatment of gastro-oesophageal reflux disease, dyspepsia, peptic ulcer disease, and Zollinger-Ellison syndrome.		4.3611magnesium saltanti-ulcer drug;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor
arbaclofen placarbil
arbaclofen placarbil: an R-baclofen prodrug; may improve the treatment of patients with gastroesophageal reflux disease, spasticity; structure in first source		5.330
azd2066
[no description available]		4.1410
ConditionIndicatedRelationship StrengthStudiesTrials
Esophageal Reflux
[description not available]		011.79176
Gastroesophageal Reflux
Retrograde flow of gastric juice (GASTRIC ACID) and/or duodenal contents (BILE ACIDS; PANCREATIC JUICE) into the distal ESOPHAGUS, commonly due to incompetence of the LOWER ESOPHAGEAL SPHINCTER.		011.79176
Fatty Liver, Nonalcoholic
[description not available]		02.3110
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.3110
Non-alcoholic Fatty Liver Disease
Fatty liver finding without excessive ALCOHOL CONSUMPTION.		02.3110
Alloxan Diabetes
[description not available]		02.1510
Sensitivity and Specificity
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)		02.110
Bilateral Headache
[description not available]		04.411
Headache
The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.		04.411
Nausea
An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.		04.411
Dysesthesia
[description not available]		03.0410
Chronic Illness
[description not available]		03.9610
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		03.9610
Hypothermia, Accidental
[description not available]		02.0510
Hypothermia
Lower than normal body temperature, especially in warm-blooded animals.		02.0510
Muscle Relaxation
That phase of a muscle twitch during which a muscle returns to a resting position.		05.2741
Esophagitis, Reflux
[description not available]		04.3911
Esophagitis, Peptic
INFLAMMATION of the ESOPHAGUS that is caused by the reflux of GASTRIC JUICE with contents of the STOMACH and DUODENUM.		04.3911