Identification

Name
Ritodrine
Accession Number
DB00867  (APRD00541)
Type
Small Molecule
Groups
Approved, Investigational
Description

Adrenergic beta-agonist used to control premature labor. [PubChem]

Structure
Thumb
Synonyms
  • DU-21220
  • Ritodrina
  • Ritodrine
  • Ritodrinium
Product Ingredients
IngredientUNIICASInChI Key
Ritodrine HydrochlorideESJ56Q60GC23239-51-2IDLSITKDRVDKRV-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Yutopar Inj 50mg/5mlLiquid10 mgIntravenousBristol Labs Division Of Bristol Myers Squibb1984-12-312001-07-30Canada
Yutopar Tab 10mgTablet10 mgOralBristol Labs Division Of Bristol Myers Squibb1984-12-312001-07-30Canada
International/Other Brands
Yutopar
Categories
UNII
I0Q6O6740J
CAS number
26652-09-5
Weight
Average: 287.3535
Monoisotopic: 287.152143543
Chemical Formula
C17H21NO3
InChI Key
IOVGROKTTNBUGK-SJCJKPOMSA-N
InChI
InChI=1S/C17H21NO3/c1-12(17(21)14-4-8-16(20)9-5-14)18-11-10-13-2-6-15(19)7-3-13/h2-9,12,17-21H,10-11H2,1H3/t12-,17-/m0/s1
IUPAC Name
4-(2-{[(1R,2S)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]amino}ethyl)phenol
SMILES
C[C@H](NCCC1=CC=C(O)C=C1)[C@H](O)C1=CC=C(O)C=C1

Pharmacology

Indication

For the treatment and prophylaxis of premature labour

Pharmacodynamics

Beta-2 adrenergic receptors are located at sympathetic neuroeffector junctions of many organs, including uterus. Ritodrine is beta-2 adrenergic agonist. It stimulates beta-2 adrenergic receptor, increases cAMP level and decreases intracellular calcium concentration. The decrease of calcium concentration leads to a relaxation of uterine smooth muscle and, therefore, a decrease in premature uterine contractions.

Mechanism of action

Ritodrine is beta-2 adrenergic agonist. It binds to beta-2 adrenergic receptors on outer membrane of myometrial cell, activates adenyl cyclase to increase the level of cAMP which decreases intracellular calcium and leads to a decrease of uterine contractions.

TargetActionsOrganism
ABeta-2 adrenergic receptor
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

~56%

Metabolism

Hepatic, by both the mother and fetus

Route of elimination
Not Available
Half life

1.7-2.6 hours

Clearance
Not Available
Toxicity

LD50=64mg/kg (mice, IV); LD50=540 mg/kg (mice, oral); LD50=85 mg/kg (rat, IV)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Ritodrine.
AcebutololThe therapeutic efficacy of Ritodrine can be decreased when used in combination with Acebutolol.
AcepromazineAcepromazine may decrease the vasoconstricting activities of Ritodrine.
AlclometasoneThe risk or severity of hypokalemia can be increased when Alclometasone is combined with Ritodrine.
AlfuzosinThe therapeutic efficacy of Ritodrine can be decreased when used in combination with Alfuzosin.
AlprenololAlprenolol may decrease the bronchodilatory activities of Ritodrine.
AmcinonideThe risk or severity of hypokalemia can be increased when Amcinonide is combined with Ritodrine.
AmineptineThe risk or severity of adverse effects can be increased when Amineptine is combined with Ritodrine.
AmitriptylineThe therapeutic efficacy of Ritodrine can be decreased when used in combination with Amitriptyline.
AmitriptylinoxideThe risk or severity of adverse effects can be increased when Amitriptylinoxide is combined with Ritodrine.
Food Interactions
Not Available

References

Synthesis Reference

Naoki Yamazaki, Yoshimasa Fukuda, Yoshiaki Shibazaki, Tetsutarou Niizato, Isao Kosugi, Shin Yoshioka, "(-)-ritodrine, therapeutic compositions and use, and method of preparation." U.S. Patent US5449694, issued July, 1992.

US5449694
General References
Not Available
External Links
Human Metabolome Database
HMDB0015005
KEGG Drug
D02359
KEGG Compound
C07239
PubChem Compound
33572
PubChem Substance
46505273
ChemSpider
30971
BindingDB
97162
ChEBI
8872
ChEMBL
CHEMBL785
Therapeutic Targets Database
DAP000937
PharmGKB
PA451258
Drugs.com
Drugs.com Drug Page
Wikipedia
Ritodrine
ATC Codes
G02CA01 — Ritodrine
MSDS
Download (48 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
4CompletedPreventionPremature Births1
4RecruitingPreventionPreterm Labor Without Delivery1
Not AvailableRecruitingTreatmentPremature Labour1

Pharmacoeconomics

Manufacturers
  • Abraxis pharmaceutical products
  • Hospira inc
  • Astrazeneca lp
Packagers
  • Solvay Pharmaceuticals
Dosage forms
FormRouteStrength
LiquidIntravenous10 mg
TabletOral10 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)88-90 °CNot Available
water solubilityCompleteNot Available
logP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.179 mg/mLALOGPS
logP1.53ALOGPS
logP1.82ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)9.15ChemAxon
pKa (Strongest Basic)9.81ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area72.72 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity83.02 m3·mol-1ChemAxon
Polarizability31.56 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9871
Blood Brain Barrier-0.8115
Caco-2 permeable-0.5546
P-glycoprotein substrateSubstrate0.692
P-glycoprotein inhibitor INon-inhibitor0.953
P-glycoprotein inhibitor IINon-inhibitor0.8732
Renal organic cation transporterNon-inhibitor0.6134
CYP450 2C9 substrateNon-substrate0.6367
CYP450 2D6 substrateSubstrate0.5054
CYP450 3A4 substrateNon-substrate0.5874
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9442
CYP450 2D6 inhibitorNon-inhibitor0.6034
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8351
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7277
Ames testNon AMES toxic0.7799
CarcinogenicityNon-carcinogens0.9177
BiodegradationNot ready biodegradable0.8862
Rat acute toxicity2.2303 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7534
hERG inhibition (predictor II)Inhibitor0.5409
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenethylamines. These are compounds containing a phenethylamine moiety, which consists of a phenyl group substituted at the second position by an ethan-1-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenethylamines
Direct Parent
Phenethylamines
Alternative Parents
Phenylpropanes / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Phenethylamine / Phenylpropane / Phenol / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / Secondary alcohol / 1,2-aminoalcohol / Secondary amine / Secondary aliphatic amine / Amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
amphetamines (CHEBI:8872)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Tanaka N, Tamai T, Mukaiyama H, Hirabayashi A, Muranaka H, Akahane S, Miyata H, Akahane M: Discovery of novel N-phenylglycine derivatives as potent and selective beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence. J Med Chem. 2001 Apr 26;44(9):1436-45. [PubMed:11311067]
  2. Schwarz MK, Page P: Preterm labour: an overview of current and emerging therapeutics. Curr Med Chem. 2003 Aug;10(15):1441-68. [PubMed:12871140]
  3. Lye SJ, Dayes BA, Freitag CL, Brooks J, Casper RF: Failure of ritodrine to prevent preterm labor in the sheep. Am J Obstet Gynecol. 1992 Nov;167(5):1399-408. [PubMed:1332478]
  4. Bianchetti A, Manara L: In vitro inhibition of intestinal motility by phenylethanolaminotetralines: evidence of atypical beta-adrenoceptors in rat colon. Br J Pharmacol. 1990 Aug;100(4):831-9. [PubMed:1976401]
  5. Lenselink DR, Kuhlmann RS, Lawrence JM, Kolesari GL: Cardiovascular teratogenicity of terbutaline and ritodrine in the chick embryo. Am J Obstet Gynecol. 1994 Aug;171(2):501-6. [PubMed:8059831]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Phosphogluconate dehydrogenase (decarboxylating) activity
Specific Function
Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
Gene Name
PGD
Uniprot ID
P52209
Uniprot Name
6-phosphogluconate dehydrogenase, decarboxylating
Molecular Weight
53139.56 Da
References
  1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Aug;25(4):476-9. doi: 10.3109/14756360903257900. [PubMed:20235752]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:26