Bromotheophylline

Overview

DrugBank ID
DB14018
Type
Small Molecule
US Approved
NO
Other Approved
YES
Clinical Trials
Phase 0
0
Phase 1
0
Phase 2
0
Phase 3
0
Phase 4
0
Therapeutic Categories
  • Diuretics
Mechanism of Action

Identification

Brand Names
Pamprin Multi-symptom, Premsyn Pms
Generic Name
Bromotheophylline
DrugBank Accession Number
DB14018
Background

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

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 259.063
Monoisotopic: 257.975238
Chemical Formula
C7H7BrN4O2
Synonyms
  • 8-Bromotheophylline

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

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination for symptomatic treatment ofPremenstrual syndromeCombination Product in combination with: Acetaminophen (DB00316), Mepyramine (DB06691)••••••••••••••••••• ••••••
Used in combination for symptomatic treatment ofPremenstrual syndromeCombination Product in combination with: Acetaminophen (DB00316)••• •••
Used in combination for symptomatic treatment ofMenstrual syndromeCombination Product in combination with: Acetaminophen (DB00316)••• •••
Treatment ofWater retention••• •••
Contraindications & Blackbox Warnings
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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

TargetActionsOrganism
AAdenosine receptor
antagonist
Humans
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.

Adverse Effects
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Toxicity

In overdose, bromotheophylline does not produce hepatic toxicity.8

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe therapeutic efficacy of 1,2-Benzodiazepine can be decreased when used in combination with Bromotheophylline.
AbacavirBromotheophylline may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbametapirThe serum concentration of Bromotheophylline can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Bromotheophylline can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Bromotheophylline can be increased when it is combined with Abiraterone.
Food Interactions
  • Drink plenty of fluids. Avoid dehydration by drinking 6-8 glasses of water daily.
  • Take with a full glass of water.

Products

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Product Ingredients
IngredientUNIICASInChI Key
PamabromUA8U0KJM72606-04-2ATOTUUBRFJHZQG-UHFFFAOYSA-N
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DiurexCapsule, liquid filled50 mg/1OralAlva-Amco Pharmacal Companies, Inc.2000-04-102022-01-31US flag
DiurexCapsule50 mg/1OralAlva-Amco Pharmacal Companies, Inc.2005-04-01Not applicableUS flag
Diurex MaxTablet, film coated50 mg/1OralAlva-Amco Pharmacal Companies, Inc.1995-12-20Not applicableUS flag
Diurex MaxTablet, film coated50 mg/1OralAlva-Amco Pharmacal Companies, Inc.2001-03-05Not applicableUS flag
Diurex Water CapletsTablet50 mgOralAlva-Amco Pharmacal Companies, Inc.2001-03-12Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ActiMol Menstrual TabletPamabrom (25 mg) + Acetaminophen (500 mg)TabletOralPHARMANIAGA MANUFACTURING BERHAD2020-09-08Not applicableMalaysia flag
BackAid MaxPamabrom (25 mg/1) + Acetaminophen (500 mg/1)Tablet, film coatedOralAlva-Amco Pharmacal Companies, Inc.1992-02-01Not applicableUS flag
Cramp TabsPamabrom (25 mg/1) + Acetaminophen (325 mg/1)TabletOralRedicare Llc2017-02-01Not applicableUS flag
Cramp TabsPamabrom (25 1/1) + Acetaminophen (325 1/1)TabletOralAdvanced First Aid, Inc.2015-08-10Not applicableUS flag
Crane Safety CrampPamabrom (25 mg/1) + Acetaminophen (325 mg/1)Tablet, film coatedOralCrane Safety LLC2020-01-172023-11-01US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
DiurexPamabrom (50 mg/1)Capsule, liquid filledOralAlva-Amco Pharmacal Companies, Inc.2000-04-102022-01-31US flag
Diurex MaxPamabrom (50 mg/1)Tablet, film coatedOralAlva-Amco Pharmacal Companies, Inc.1995-12-20Not applicableUS flag
PamabromPamabrom (50 mg/1)Capsule, liquid filledOralWalgreens Company2020-11-24Not applicableUS flag

Categories

ATC Codes
R03DA20 — Combinations of xanthines
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
FZG87K1MQ6
CAS number
10381-75-6
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

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. [Article]
  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. [Article]
  3. FDA Submission [Link]
  4. Health Canada [Link]
  5. FDA history [Link]
  6. Dailymed [Link]
  7. CNKI [Link]
  8. Annexpublishers [Link]
ChemSpider
11315
BindingDB
50045345
RxNav
1546386
ChEMBL
CHEMBL316160
ZINC
ZINC000100005670
MSDS
Download (47.6 KB)

Clinical Trials

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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
TabletOral50 mg/1
Tablet, coatedOral
Tablet, film coatedOral25 mg
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/MSsplash10-0a4i-0090000000-64e1f352a8b3b078f4fd
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0290000000-e66daf8a4433105a0fd7
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0pi0-0490000000-850278f0d18c82c8d997
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a6r-5490000000-b25cffc46a538e71e183
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0kft-1900000000-6aa84fe37ce908fd5240
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9200000000-885993cb246b81efc5fe
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-137.12422
predicted
DeepCCS 1.0 (2019)
[M+H]+139.51979
predicted
DeepCCS 1.0 (2019)
[M+Na]+146.31384
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Specific Function
G protein-coupled adenosine receptor activity

Components:
References
  1. 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. [Article]

Enzymes

Kind
Protein
Organism
Humans
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
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
Specific Function
aromatase activity
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58406.915 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Theophylline metabolic pathway [Link]
  6. CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine [File]

Drug created at April 27, 2018 01:52 / Updated at November 09, 2024 06:00