Basic Info

Common NameDiphenhydramine(F04779)
2D Structure
Description

Diphenhydramine is a histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. -- Pubchem; Pseudoephedrine is a phenethylamine, and an isomer of ephedrine. Pseudoephedrine is the International Nonproprietary Name (INN) of the (1S,2S)- diastereomer of ephedrine (which has 1R,2S- configuration). Other names are (+)-pseudoephedrine and D-pseudoephedrine (Reynolds, 1989). The enantiomer (-)-(1R,2R)-Pseudoephedrine has fewer side-effects, fewer central nervous system (CNS) stimulatory effects, does not reduce to d-methamphetamine, yet retains its efficacy as a decongestant. However, the patent holder for (-)-Pseudoephedrine (Pfizer/Warner-Lambert) has not yet sought or received government approval for its sale to the public.(US Patent 6,495,529); Treatment for urinary incontinence is an unlabeled use for these medications. Unlabeled use means doctors can use the medication to treat a condition other than that for which it was first approved by the U.S. Food and Drug Administration (FDA). These medications are approved by the FDA for the treatment of nasal congestion caused by colds or allergies. However it has also been successful in treating stress incontinence by increasing the pressure (tension) exerted by the muscles of the bladder neck and the urethra, which helps retain the urine within the bladder. Despite being one of the oldest antihistamines on the market, it is by and large the most effective antihistamine available, either by prescription or over-the-counter, and has been shown to exceed the effectiveness of even the latest prescription drugs. Consequently, it is frequently used when an allergic reaction requires fast, effective reversal of the (often dangerous) effects of a massive histamine release. However, it is not always the drug of choice for treating allergies. Like many other first generation antihistamines, is also a potent anticholinergic agent. This leads to profound drowsiness as a very common side-effect, along with the possibilities of motor impairment (ataxia), dry mouth and throat, flushed skin, rapid or irregular heartbeat (tachycardia), blurred vision at near point due to lack of accommodation (cycloplegia), abnormal sensitivity to bright light (photophobia), pupil dilatation, urinary retention, constipation, difficulty concentrating, short-term memory loss, visual disturbances, hallucinations, confusion, erectile dysfunction, and delirium. -- Wikipedia;.

FRCD IDF04779
CAS Number58-73-1
PubChem CID3100
FormulaC17H21NO
IUPAC Name

2-benzhydryloxy-N,N-dimethylethanamine

InChI Key

ZZVUWRFHKOJYTH-UHFFFAOYSA-N

InChI

InChI=1S/C17H21NO/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3

Canonical SMILES

CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2

Isomeric SMILES

CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2

WikipediaDiphenhydramine
Synonyms
        
            Probedryl
        
            diphenhydramine
        
            58-73-1
        
            Benadryl
        
            Benzhydramine
        
            Alledryl
        
            Dihidral
        
            Antistominum
        
            Benzhydraminum
        
            Benzhydroamina
        
Classifies
                

                  
                    Predicted: Pollutant
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassBenzenoids
ClassBenzene and substituted derivatives
SubclassDiphenylmethanes
Intermediate Tree NodesNot available
Direct ParentDiphenylmethanes
Alternative Parents
Molecular FrameworkAromatic homomonocyclic compounds
SubstituentsDiphenylmethane - Benzylether - Tertiary aliphatic amine - Tertiary amine - Ether - Dialkyl ether - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Amine - Aromatic homomonocyclic compound
DescriptionThis compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.

Properties

Property NameProperty Value
Molecular Weight255.361
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count2
Rotatable Bond Count6
Complexity211
Monoisotopic Mass255.162
Exact Mass255.162
XLogP3.3
Formal Charge0
Heavy Atom Count19
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9381
Human Intestinal AbsorptionHIA+0.9898
Caco-2 PermeabilityCaco2+0.8744
P-glycoprotein SubstrateSubstrate0.6211
P-glycoprotein InhibitorNon-inhibitor0.6632
Non-inhibitor0.8381
Renal Organic Cation TransporterInhibitor0.7752
Distribution
Subcellular localizationMitochondria0.5148
Metabolism
CYP450 2C9 SubstrateNon-substrate0.7897
CYP450 2D6 SubstrateSubstrate0.8919
CYP450 3A4 SubstrateSubstrate0.6173
CYP450 1A2 InhibitorInhibitor0.8306
CYP450 2C9 InhibitorNon-inhibitor0.9144
CYP450 2D6 InhibitorInhibitor0.8932
CYP450 2C19 InhibitorNon-inhibitor0.9039
CYP450 3A4 InhibitorNon-inhibitor0.9340
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.7293
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.5360
Inhibitor0.6318
AMES ToxicityNon AMES toxic0.9132
CarcinogensNon-carcinogens0.6495
Fish ToxicityHigh FHMT0.6983
Tetrahymena Pyriformis ToxicityLow TPT0.5301
Honey Bee ToxicityLow HBT0.6179
BiodegradationNot ready biodegradable0.9253
Acute Oral ToxicityII0.7442
Carcinogenicity (Three-class)Non-required0.6998

Model Value Unit
Absorption
Aqueous solubility-2.7839LogS
Caco-2 Permeability1.6953LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.7846LD50, mol/kg
Fish Toxicity1.3365pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.3390pIGC50, ug/L

References

TitleJournalDatePubmed ID
Biodistribution of diphenhydramine in reproductive organs in an overdose case.Hum Cell2017 Apr27838883
A Quantitative Analysis of OnabotulinumtoxinA, AbobotulinumtoxinA, andIncobotulinumtoxinA: A Randomized, Double-Blind, Prospective Clinical Trial ofComparative Dynamic Strain Reduction.Plast Reconstr Surg2016 May27119918
Pregnancy outcomes following exposure to onabotulinumtoxinA.Pharmacoepidemiol Drug Saf2016 Feb26635276
Botulinum Toxin to Treat Neurogenic Bladder.Semin Neurol2016 Feb26866490
Brief Toxicology Observation: What Kind of Burger Did This Patient Eat?J Med Toxicol2015 Sep25672251
In vitro detection of cardiotoxins or neurotoxins affecting ion channels or pumps using beating cardiomyocytes as alternative for animal testing.Toxicol In Vitro2015 Mar25479353
Analysis of botulinum toxin products and litigation in the United States.Dermatol Surg2013 Nov23464535
Practical applications of a new botulinum toxin.J Drugs Dermatol2010 Mar20361474
Botulinum neurotoxin type A-ABO (Dysport): clinical indications and practiceguide.Aesthet Surg J2009 Nov19945008
Injectable botulinum toxin as a treatment for plantar hyperhidrosis: a case study.J Am Podiatr Med Assoc2008 Mar-Apr18347128
Gastric electrical stimulation: an evidence-based analysis.Ont Health Technol Assess Ser200623074486
Disinfection efficacy of contact lens care solutions against ocular pathogens.CLAO J2001 Jan11215601
Potentiation of anaphylaxis in guinea pig ileal mucosa by a selective delta-opioid receptor agonist.Eur J Pharmacol1999 Aug 2010499375
Botulinum toxin use in pediatric esophageal achalasia: a case report.J Pediatr Surg1997 Jun9200100
Evidence that histamine is the causative toxin of scombroid-fish poisoning.N Engl J Med1991 Mar 141997836
Mucosal mast cells and the intestinal epithelium.Adv Exp Med Biol19873687546
Discriminative-stimulus effects of midazolam in squirrel monkeys: comparison with other drugs and antagonism by Ro 15-1788.J Pharmacol Exp Ther1985 Nov2932547
Experimental Escherichia coli mastitis in cattle, its pathogenisis and treatment.Tijdschr Diergeneeskd1973 Apr 154134508

Targets

General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
References
  1. Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
General Function:
Histamine receptor activity
Specific Function:
The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization.
Gene Name:
HRH3
Uniprot ID:
Q9Y5N1
Molecular Weight:
48670.81 Da
References
  1. Liu C, Ma X, Jiang X, Wilson SJ, Hofstra CL, Blevitt J, Pyati J, Li X, Chai W, Carruthers N, Lovenberg TW: Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6. [11179434 ]
General Function:
Histamine receptor activity
Specific Function:
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
Gene Name:
HRH4
Uniprot ID:
Q9H3N8
Molecular Weight:
44495.375 Da
References
  1. Wagner E, Wittmann HJ, Elz S, Strasser A: Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH(1)R, but low affinity to hH(4)R. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6274-80. doi: 10.1016/j.bmcl.2011.09.001. Epub 2011 Sep 8. [21944853 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
References
  1. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
References
  1. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
References
  1. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da
References
  1. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Mechanism of Action:
Diphenhydramine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding.
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]