Diphenhydramine
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Basic Info
Common Name | Diphenhydramine(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 ID | F04779 |
CAS Number | 58-73-1 |
PubChem CID | 3100 |
Formula | C17H21NO |
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 |
Wikipedia | Diphenhydramine |
Synonyms | Probedryl diphenhydramine 58-73-1 Benadryl Benzhydramine Alledryl Dihidral Antistominum Benzhydraminum Benzhydroamina |
Classifies | Predicted: Pollutant |
Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
Kingdom | Organic compounds |
Superclass | Benzenoids |
Class | Benzene and substituted derivatives |
Subclass | Diphenylmethanes |
Intermediate Tree Nodes | Not available |
Direct Parent | Diphenylmethanes |
Alternative Parents | |
Molecular Framework | Aromatic homomonocyclic compounds |
Substituents | Diphenylmethane - 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 |
Description | This 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 Name | Property Value |
---|---|
Molecular Weight | 255.361 |
Hydrogen Bond Donor Count | 0 |
Hydrogen Bond Acceptor Count | 2 |
Rotatable Bond Count | 6 |
Complexity | 211 |
Monoisotopic Mass | 255.162 |
Exact Mass | 255.162 |
XLogP | 3.3 |
Formal Charge | 0 |
Heavy Atom Count | 19 |
Defined Atom Stereocenter Count | 0 |
Undefined Atom Stereocenter Count | 0 |
Defined Bond Stereocenter Count | 0 |
Undefined Bond Stereocenter Count | 0 |
Isotope Atom Count | 0 |
Covalently-Bonded Unit Count | 1 |
ADMET
Model | Result | Probability |
---|---|---|
Absorption | ||
Blood-Brain Barrier | BBB+ | 0.9381 |
Human Intestinal Absorption | HIA+ | 0.9898 |
Caco-2 Permeability | Caco2+ | 0.8744 |
P-glycoprotein Substrate | Substrate | 0.6211 |
P-glycoprotein Inhibitor | Non-inhibitor | 0.6632 |
Non-inhibitor | 0.8381 | |
Renal Organic Cation Transporter | Inhibitor | 0.7752 |
Distribution | ||
Subcellular localization | Mitochondria | 0.5148 |
Metabolism | ||
CYP450 2C9 Substrate | Non-substrate | 0.7897 |
CYP450 2D6 Substrate | Substrate | 0.8919 |
CYP450 3A4 Substrate | Substrate | 0.6173 |
CYP450 1A2 Inhibitor | Inhibitor | 0.8306 |
CYP450 2C9 Inhibitor | Non-inhibitor | 0.9144 |
CYP450 2D6 Inhibitor | Inhibitor | 0.8932 |
CYP450 2C19 Inhibitor | Non-inhibitor | 0.9039 |
CYP450 3A4 Inhibitor | Non-inhibitor | 0.9340 |
CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.7293 |
Excretion | ||
Toxicity | ||
Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.5360 |
Inhibitor | 0.6318 | |
AMES Toxicity | Non AMES toxic | 0.9132 |
Carcinogens | Non-carcinogens | 0.6495 |
Fish Toxicity | High FHMT | 0.6983 |
Tetrahymena Pyriformis Toxicity | Low TPT | 0.5301 |
Honey Bee Toxicity | Low HBT | 0.6179 |
Biodegradation | Not ready biodegradable | 0.9253 |
Acute Oral Toxicity | II | 0.7442 |
Carcinogenicity (Three-class) | Non-required | 0.6998 |
Model | Value | Unit |
---|---|---|
Absorption | ||
Aqueous solubility | -2.7839 | LogS |
Caco-2 Permeability | 1.6953 | LogPapp, cm/s |
Distribution | ||
Metabolism | ||
Excretion | ||
Toxicity | ||
Rat Acute Toxicity | 2.7846 | LD50, mol/kg |
Fish Toxicity | 1.3365 | pLC50, mg/L |
Tetrahymena Pyriformis Toxicity | 0.3390 | pIGC50, ug/L |
References
Title | Journal | Date | Pubmed ID |
---|---|---|---|
Biodistribution of diphenhydramine in reproductive organs in an overdose case. | Hum Cell | 2017 Apr | 27838883 |
A Quantitative Analysis of OnabotulinumtoxinA, AbobotulinumtoxinA, andIncobotulinumtoxinA: A Randomized, Double-Blind, Prospective Clinical Trial ofComparative Dynamic Strain Reduction. | Plast Reconstr Surg | 2016 May | 27119918 |
Pregnancy outcomes following exposure to onabotulinumtoxinA. | Pharmacoepidemiol Drug Saf | 2016 Feb | 26635276 |
Botulinum Toxin to Treat Neurogenic Bladder. | Semin Neurol | 2016 Feb | 26866490 |
Brief Toxicology Observation: What Kind of Burger Did This Patient Eat? | J Med Toxicol | 2015 Sep | 25672251 |
In vitro detection of cardiotoxins or neurotoxins affecting ion channels or pumps using beating cardiomyocytes as alternative for animal testing. | Toxicol In Vitro | 2015 Mar | 25479353 |
Analysis of botulinum toxin products and litigation in the United States. | Dermatol Surg | 2013 Nov | 23464535 |
Practical applications of a new botulinum toxin. | J Drugs Dermatol | 2010 Mar | 20361474 |
Botulinum neurotoxin type A-ABO (Dysport): clinical indications and practiceguide. | Aesthet Surg J | 2009 Nov | 19945008 |
Injectable botulinum toxin as a treatment for plantar hyperhidrosis: a case study. | J Am Podiatr Med Assoc | 2008 Mar-Apr | 18347128 |
Gastric electrical stimulation: an evidence-based analysis. | Ont Health Technol Assess Ser | 2006 | 23074486 |
Disinfection efficacy of contact lens care solutions against ocular pathogens. | CLAO J | 2001 Jan | 11215601 |
Potentiation of anaphylaxis in guinea pig ileal mucosa by a selective delta-opioid receptor agonist. | Eur J Pharmacol | 1999 Aug 20 | 10499375 |
Botulinum toxin use in pediatric esophageal achalasia: a case report. | J Pediatr Surg | 1997 Jun | 9200100 |
Evidence that histamine is the causative toxin of scombroid-fish poisoning. | N Engl J Med | 1991 Mar 14 | 1997836 |
Mucosal mast cells and the intestinal epithelium. | Adv Exp Med Biol | 1987 | 3687546 |
Discriminative-stimulus effects of midazolam in squirrel monkeys: comparison with other drugs and antagonism by Ro 15-1788. | J Pharmacol Exp Ther | 1985 Nov | 2932547 |
Experimental Escherichia coli mastitis in cattle, its pathogenisis and treatment. | Tijdschr Diergeneeskd | 1973 Apr 15 | 4134508 |
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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]