Identification

Name
Bromotheophylline
Accession Number
DB14018
Type
Small Molecule
Groups
Approved
Description

Bromotheophylline is the active moiety of pamabrom, a mixture of 2-amino-2-methyl-propanol and bromotheophylline. From this mixture, bromotheophylline acts as a weak diuretic that has been used along with some analgesics to relieve the symptoms of premenstrual syndrome.[1] Bromotheophylline is categorized on the FDA as a drug substance with an inactive state since March, 1980.[3] It is also approved by Health Canada to be used alone or in combination with Acetaminophen in OTC products.[4]

Structure
Thumb
Synonyms
  • 8-Bromotheophylline
Product Ingredients
IngredientUNIICASInChI Key
PamabromUA8U0KJM72606-04-2ATOTUUBRFJHZQG-UHFFFAOYSA-N
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DiurexCapsule50 mg/1OralAlva Amco Pharmacal Companies, Inc.2005-04-01Not applicableUs
DiurexCapsule, liquid filled50 mg/1OralAlva Amco Pharmacal Companies, Inc.2000-04-10Not applicableUs
Diurex MaxTablet, film coated50 mg/1OralAlva Amco Pharmacal Companies, Inc.1995-12-20Not applicableUs
Diurex Water CapletsTablet50 mgOralAlva Amco Pharmacal Companies, Inc.2001-03-12Not applicableCanada
Diurex Water CapsulesCapsule50 mgOralAlva Amco Pharmacal Companies, Inc.Not applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
BackAid MaxPamabrom (25 mg/1) + Acetaminophen (500 mg/1)Tablet, film coatedOralAlva-Amco Pharmacal Companies, Inc.1992-02-01Not applicableUs
Cramp TabsPamabrom (25 mg/1) + Acetaminophen (325 mg/1)TabletOralRedicare Llc2017-02-01Not applicableUs
Cramp TabsPamabrom (25 1/1) + Acetaminophen (325 1/1)TabletOralAdvanced First Aid, Inc.2015-08-10Not applicableUs
Extra Strength Multi-symptom Pms ReliefPamabrom (25 mg) + Acetaminophen (500 mg) + Mepyramine maleate (15 mg)TabletOralVita Health Products Inc1999-06-22Not applicableCanada
Extra Strength Tylenol Menstrual CapletsPamabrom (25 mg) + Acetaminophen (500 mg) + Mepyramine maleate (15 mg)TabletOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc1999-01-272016-01-22Canada
Fem ReliefPamabrom (25 mg/1) + Acetaminophen (325 mg/1)TabletOralHoneywell Safety Products USA, Inc2012-02-152017-01-01Us
Fem ReliefPamabrom (25 mg/1) + Acetaminophen (325 mg/1)TabletOralHoneywell Safety Products USA, Inc2017-01-01Not applicableUs
FemadrinePamabrom (25 1/1) + Acetaminophen (325 1/1)TabletOralAfassco Inc.2016-10-25Not applicableUs
Green Guard PMS ReliefPamabrom (25 mg/1) + Acetaminophen (325 mg/1)Tablet, film coatedOralUnifirst First Aid Corporation2008-12-30Not applicableUs
Leader PremenstrualPamabrom (25 mg/1) + Acetaminophen (500 mg/1) + Mepyramine maleate (15 mg/1)CapsuleOralCardinal Health2012-02-28Not applicableUs
Categories
UNII
FZG87K1MQ6
CAS number
10381-75-6
Weight
Average: 259.063
Monoisotopic: 257.975238
Chemical Formula
C7H7BrN4O2
InChI Key
SKTFQHRVFFOHTQ-UHFFFAOYSA-N
InChI
InChI=1S/C7H7BrN4O2/c1-11-4-3(9-6(8)10-4)5(13)12(2)7(11)14/h1-2H3,(H,9,10)
IUPAC Name
8-bromo-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CN1C2=C(NC(Br)=N2)C(=O)N(C)C1=O

Pharmacology

Indication

Bromotheophylline is used as a diuretic and also, in combination with Acetaminophen, it is used for the relief of temporary water weight gain, bloating, swelling and full feeling associated with the premenstrual and menstrual periods.[5]

Associated Conditions
Pharmacodynamics

Bromotheophylline diuretic action will produce an immediate increase in urination frequency. This effect aids in the relief of bloating and menstrual pain.[1] This diuretic function is performed by the an increase in glomerular filtration and a potential effect in the tubular reabsorption as it is established that the administration of these agents produce a rise in the urinary concentration of sodium a chloride and thus, an increase in their rates of excretion.[2]

Mechanism of action

Bromotheophylline is part of the group of the xanthines. As part of this group, it is thought that bromotheophylline increases the permeability of the renal tubule, increases glomerular filtration rate and inhibits the sodium reabsorption in the proximal tubule.[2] It is thought but not confirmed that pamabrom as a mixture seems to have an additional mechanism of action in which the presence of 2-amino-2-methyl-1-propanol produces the suppression of the antidiuretic hormone in the posterior pituitary gland.[8]

Absorption

When administered after one single oral dosage, bromotheophylline is rapidly absorbed and it reaches a maximal plasma concentration of 2.5 mg/L in 0.78 hours. The mean residence time is registered to be of 12 hours with an AUC in the first 8 hours of 27 mg.h/L.[7]

Volume of distribution

This pharmacokinetic property has not been determined.

Protein binding

This pharmacokinetic property has not been determined.

Metabolism

This pharmacokinetic property has not been determined.

Route of elimination

This pharmacokinetic property has not been determined.

Half life

The apparent elimination half-life is registered to be 21.35 hours.[8]

Clearance

This pharmacokinetic property has not been determined.

Toxicity

In overdose, bromotheophylline does not produce hepatic toxicity.[8]

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe serum concentration of Bromotheophylline can be increased when it is combined with (R)-warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Bromotheophylline.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Bromotheophylline.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Bromotheophylline.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Bromotheophylline.
3,5-diiodothyropropionic acidThe serum concentration of Bromotheophylline can be increased when it is combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Bromotheophylline.
6-Deoxyerythronolide BThe metabolism of Bromotheophylline can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe serum concentration of Bromotheophylline can be increased when it is combined with 6-O-benzylguanine.
7-DeazaguanineThe serum concentration of 7-Deazaguanine can be increased when it is combined with Bromotheophylline.
Food Interactions
Not Available

References

General References
  1. Shah U, Kavad M, Raval M: Development and Validation of Stability-indicating RP-HPLC Method for Estimation of Pamabrom in Tablets. Indian J Pharm Sci. 2014 May;76(3):198-202. [PubMed:25035530]
  2. MUDGE GH, WEINER IM: The mechanism of action of mercurial and xanthine diuretics. Ann N Y Acad Sci. 1958 Feb 3;71(4):344-54. [PubMed:13583790]
  3. FDA Submission [Link]
  4. Health Canada [Link]
  5. FDA history [Link]
  6. Dailymed [Link]
  7. CNKI [Link]
  8. Annexpublishers [Link]
External Links
ChemSpider
11315
BindingDB
50045345
ChEMBL
CHEMBL316160
ATC Codes
R03DA20 — Combinations of xanthines
AHFS Codes
  • 40:28.00 — Diuretics
MSDS
Download (47.6 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral50 mg/1
Capsule, liquid filledOral50 mg/1
Tablet, film coatedOral50 mg/1
TabletOral50 mg
CapsuleOral50 mg
CapsuleOral
Tablet, film coatedOral
Tablet, coatedOral
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)295-316 ºC'MSDS'
boiling point (°C)Decomposes at 300 ºC'MSDS'
water solubilitySolubleShah U., Kavad M. and Raval M. Indian J Pharm Sci. (2014)
pKa5.45Brittain H. Profiles of drug substances, excipients and related methodology. (2007)
Predicted Properties
PropertyValueSource
Water Solubility3.92 mg/mLALOGPS
logP0.23ALOGPS
logP0.29ChemAxon
logS-1.8ALOGPS
pKa (Strongest Acidic)5.58ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.3 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity52.56 m3·mol-1ChemAxon
Polarizability20.67 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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

Classification
Not classified

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Curator comments
This enzyme listing is based on pharmacokinetic data for methylxanthines as a drug class. Methylxanthines are metabolized by CYP1A2. This drug is a methylxanthine and is therefore assumed to be metabolized by this enzyme.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Thorn CF, Aklillu E, McDonagh EM, Klein TE, Altman RB: PharmGKB summary: caffeine pathway. Pharmacogenet Genomics. 2012 May;22(5):389-95. doi: 10.1097/FPC.0b013e3283505d5e. [PubMed:22293536]
  2. Buters JT, Tang BK, Pineau T, Gelboin HV, Kimura S, Gonzalez FJ: Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2. Pharmacogenetics. 1996 Aug;6(4):291-6. [PubMed:8873215]
  3. Hakooz NM: Caffeine metabolic ratios for the in vivo evaluation of CYP1A2, N-acetyltransferase 2, xanthine oxidase and CYP2A6 enzymatic activities. Curr Drug Metab. 2009 May;10(4):329-38. [PubMed:19519341]
  4. Rasmussen BB, Brosen K: Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans. Ther Drug Monit. 1996 Jun;18(3):254-62. [PubMed:8738764]
  5. Theophylline metabolic pathway [Link]
  6. CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine [File]

Drug created on April 26, 2018 19:52 / Updated on November 18, 2018 13:32