This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
8-chlorotheophylline
Accession Number
DB14132
Type
Small Molecule
Groups
Experimental
Description

8-Chlorotheophylline is a stimulant drug of the xanthine chemical class, with physiological effects similar to caffeine. Its main use is in combination with Diphenhydramine as the antiemetic drug Dimenhydrinate. The stimulant properties of 8-chlorotheophylline are thought to ward off the drowsiness caused by diphenhydramine's anti-histamine activity in the central nervous system.

8-chlorotheophylline produces a number of effects including nervousness, restlessness, insomnia, headache, and nausea, which are primarily attributed to its ability to block the adenosine receptor [1, 2]. Because adenosine causes a decrease in neuronal firing, blockade of the adenosine receptor causes the reverse effect resulting in excitation.

Structure
Thumb
Synonyms
  • 1,3-dimethyl-8-chloroxanthine
  • 8-chloro-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione
  • Chlorotheophylline
  • Chlortheophylline
Categories
UNII
GE2UA340FM
CAS number
85-18-7
Weight
Average: 214.609
Monoisotopic: 214.025753195
Chemical Formula
C7H7ClN4O2
InChI Key
RYIGNEOBDRVTHA-UHFFFAOYSA-N
InChI
InChI=1S/C7H7ClN4O2/c1-11-4-3(9-6(8)10-4)5(13)12(2)7(11)14/h1-2H3,(H,9,10)
IUPAC Name
8-chloro-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione
SMILES
CN1C2=C(NC(Cl)=N2)C(=O)N(C)C1=O

Pharmacology

Indication

When used in combination with Diphenhydramine as the antiemetic Dimenhydrinate, 8-chlorotheophylline is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness.

Pharmacodynamics
Not Available
Mechanism of action

8-chlorotheophylline produces a number of effects including nervousness, restlessness, insomnia, headache, and nausea, which are primarily attributed to its ability to block the adenosine receptor [1, 2]. Because adenosine causes a decrease in neuronal firing, blockade of the adenosine receptor causes the reverse effect resulting in excitation.

TargetActionsOrganism
AAdenosine receptor A2a
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe serum concentration of 8-chlorotheophylline 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 8-chlorotheophylline.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with 8-chlorotheophylline.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with 8-chlorotheophylline.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with 8-chlorotheophylline.
3,5-diiodothyropropionic acidThe serum concentration of 8-chlorotheophylline 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 8-chlorotheophylline.
6-Deoxyerythronolide BThe metabolism of 8-chlorotheophylline can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe serum concentration of 8-chlorotheophylline 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 8-chlorotheophylline.
Food Interactions
Not Available

References

General References
  1. Spealman RD: Psychomotor stimulant effects of methylxanthines in squirrel monkeys: relation to adenosine antagonism. Psychopharmacology (Berl). 1988;95(1):19-24. [PubMed:3133696]
  2. Halpert AG, Olmstead MC, Beninger RJ: Mechanisms and abuse liability of the anti-histamine dimenhydrinate. Neurosci Biobehav Rev. 2002 Jan;26(1):61-7. [PubMed:11835984]
External Links
ChemSpider
10211
BindingDB
50331852
ChEBI
59771
ChEMBL
CHEMBL88611
HET
H33
Wikipedia
8-Chlorotheophylline
PDB Entries
2uy3

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility9.41 mg/mLALOGPS
logP0.84ALOGPS
logP0.14ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)5.14ChemAxon
pKa (Strongest Basic)-3.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.3 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity49.96 m3·mol-1ChemAxon
Polarizability19.37 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
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Identical protein binding
Specific Function
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name
ADORA2A
Uniprot ID
P29274
Uniprot Name
Adenosine receptor A2a
Molecular Weight
44706.925 Da
References
  1. Halpert AG, Olmstead MC, Beninger RJ: Mechanisms and abuse liability of the anti-histamine dimenhydrinate. Neurosci Biobehav Rev. 2002 Jan;26(1):61-7. [PubMed:11835984]
  2. Spealman RD: Psychomotor stimulant effects of methylxanthines in squirrel monkeys: relation to adenosine antagonism. Psychopharmacology (Berl). 1988;95(1):19-24. [PubMed:3133696]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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. Coleman J., Cox A. and Cowley N. (2011). Side Effects of Drugs Annual. Elsevier.

Drug created on June 26, 2018 10:45 / Updated on November 02, 2018 07:50