Synonym
Diphenhydramine citrate
IUPAC/Chemical Name
(2-(Diphenylmethoxy)ethyl)dimethylammonium dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate
InChi Key
SPCKHVPPRJWQRZ-UHFFFAOYSA-N
InChi Code
InChI=1S/C17H21NO.C6H8O7/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16;7-3(8)1-6(13,5(11)12)2-4(9)10/h3-12,17H,13-14H2,1-2H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
SMILES Code
C[NH+](CCOC(C1=CC=CC=C1)C2=CC=CC=C2)C.O=C(CC(C(O)=O)(O)CC([O-])=O)O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Diphenhydramine hydrochloride is a first-generation histamine H1-receptor antagonist with anti-cholinergic effect.
In vitro activity:
Exogenous histamine did not alter the proliferation or viability of these cells. In contrast, diphenhydramine induced apoptosis in a dose- and time-dependent manner in both cell lines, whereas cimetidine failed to induce significant effects at similar concentrations. Diphenhydramine-induced apoptosis was evaluated in terms of morphology, flow cytometry, and the release of cytochrome c to the cytosol.
Reference: Oncol Res. 2004;14(7-8):363-72. https://pubmed.ncbi.nlm.nih.gov/15301427/
In vivo activity:
Results of the study suggest that DPM (diphenhydramine) causes reduction in CE and prevents neuronal degeneration. It also causes reduction in inflammation and oxidative stress in a dose-dependent manner. The level of Bax was found to be elevated, together with reduction in the Bcl-2 level in the DPM-treated rat group.
Reference: Pharmacology. 2020;105(1-2):47-53. https://pubmed.ncbi.nlm.nih.gov/31553997/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
447.48
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Hamano H, Ikeda Y, Goda M, Fukushima K, Kishi S, Chuma M, Yamashita M, Niimura T, Takechi K, Imanishi M, Zamami Y, Horinouchi Y, Izawa-Ishizawa Y, Miyamoto L, Ishizawa K, Fujino H, Tamaki T, Aihara KI, Tsuchiya K. Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity. Kidney Int. 2021 Apr;99(4):885-899. doi: 10.1016/j.kint.2020.10.041. Epub 2020 Dec 9. PMID: 33307103.
2. Jangi SM, Asumendi A, Arlucea J, Nieto N, Perez-Yarza G, Morales MC, de la Fuente-Pinedo M, Boyano MD. Apoptosis of human T-cell acute lymphoblastic leukemia cells by diphenhydramine, an H1 histamine receptor antagonist. Oncol Res. 2004;14(7-8):363-72. doi: 10.3727/0965040041292369. PMID: 15301427.
3. Pan W, Cao Z, Liu D, Jiao Y. Protective Effect of Diphenhydramine against Traumatic Brain Injury in Rats via Modulation of Oxidative Stress and Inflammation. Pharmacology. 2020;105(1-2):47-53. doi: 10.1159/000502767. Epub 2019 Sep 25. PMID: 31553997.
4. Or CR, Su HL, Lee WC, Yang SY, Ho C, Chang CC. Diphenhydramine induces melanoma cell apoptosis by suppressing STAT3/MCL-1 survival signaling and retards B16-F10 melanoma growth in vivo. Oncol Rep. 2016 Dec;36(6):3465-3471. doi: 10.3892/or.2016.5201. Epub 2016 Oct 25. PMID: 27779705.
In vitro protocol:
1. Hamano H, Ikeda Y, Goda M, Fukushima K, Kishi S, Chuma M, Yamashita M, Niimura T, Takechi K, Imanishi M, Zamami Y, Horinouchi Y, Izawa-Ishizawa Y, Miyamoto L, Ishizawa K, Fujino H, Tamaki T, Aihara KI, Tsuchiya K. Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity. Kidney Int. 2021 Apr;99(4):885-899. doi: 10.1016/j.kint.2020.10.041. Epub 2020 Dec 9. PMID: 33307103.
2. Jangi SM, Asumendi A, Arlucea J, Nieto N, Perez-Yarza G, Morales MC, de la Fuente-Pinedo M, Boyano MD. Apoptosis of human T-cell acute lymphoblastic leukemia cells by diphenhydramine, an H1 histamine receptor antagonist. Oncol Res. 2004;14(7-8):363-72. doi: 10.3727/0965040041292369. PMID: 15301427.
In vivo protocol:
1. Pan W, Cao Z, Liu D, Jiao Y. Protective Effect of Diphenhydramine against Traumatic Brain Injury in Rats via Modulation of Oxidative Stress and Inflammation. Pharmacology. 2020;105(1-2):47-53. doi: 10.1159/000502767. Epub 2019 Sep 25. PMID: 31553997.
2. Or CR, Su HL, Lee WC, Yang SY, Ho C, Chang CC. Diphenhydramine induces melanoma cell apoptosis by suppressing STAT3/MCL-1 survival signaling and retards B16-F10 melanoma growth in vivo. Oncol Rep. 2016 Dec;36(6):3465-3471. doi: 10.3892/or.2016.5201. Epub 2016 Oct 25. PMID: 27779705.
1: Varma A, Ford L, Patel N, Vale JA. Elimination half-life of diphenhydramine in overdose. Clin Toxicol (Phila). 2017 Jul;55(6):615-616. doi: 10.1080/15563650.2017.1296153. Epub 2017 Mar 28. PMID: 28349707.
2: Palmer RB, Reynolds KM, Banner W, Bond GR, Kauffman RE, Paul IM, Green JL, Dart RC. Adverse events associated with diphenhydramine in children, 2008-2015. Clin Toxicol (Phila). 2020 Feb;58(2):99-106. doi: 10.1080/15563650.2019.1609683. Epub 2019 May 7. PMID: 31062642.
3: Abella BS, Berger WE, Blaiss MS, Stiell IG, Herres JP, Moellman JJ, Suner S, Kessler A, Klausner HA, Caterino JM, Du J. Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial. Ann Emerg Med. 2020 Oct;76(4):489-500. doi: 10.1016/j.annemergmed.2020.05.025. Epub 2020 Jul 9. PMID: 32653333.
4: Garnett WR. Diphenhydramine. Am Pharm. 1986 Feb;NS26(2):35-40. doi: 10.1016/s0095-9561(16)38634-0. PMID: 3962845.
5: Diphenhydramine, dimenhydrinate: misuse. Prescrire Int. 2015 Nov;24(165):270. PMID: 26688907.
6: Dahal A, Neupane R, Boddu SH, Renukuntla J, Khupse R, Dudley R. Percutaneous Absorption of Lorazepam, Diphenhydramine Hydrochloride, and Haloperidol from ABH Gel. Int J Pharm Compd. 2020 Mar-Apr;24(2):168-175. PMID: 32196480.
7: Rao DD, Sait SS, Mukkanti K. Development and validation of an UPLC method for rapid determination of ibuprofen and diphenhydramine citrate in the presence of impurities in combined dosage form. J Chromatogr Sci. 2011 Apr;49(4):281-6. doi: 10.1093/chrsci/49.4.281. PMID: 21439118.
8: Shepherd G. Diphenhydramine dose response. Clin Toxicol (Phila). 2011 Jan;49(1):57; author reply 57. doi: 10.3109/15563650.2010.550583. PMID: 21288155.
9: Björnsdóttir I, Einarson TR, Gudmundsson LS, Einarsdóttir RA. Efficacy of diphenhydramine against cough in humans: a review. Pharm World Sci. 2007 Dec;29(6):577-83. doi: 10.1007/s11096-007-9122-2. Epub 2007 May 8. PMID: 17486423.
10: Chen A, Loquias EJ, Roshan R, Levene R, Zelhof R, Hickey T, Cooney GA, Gonzalez F. Safe Use of Subcutaneous Diphenhydramine in the Inpatient Hospice Unit. Am J Hosp Palliat Care. 2017 Dec;34(10):954-957. doi: 10.1177/1049909116668160. Epub 2016 Sep 13. PMID: 27625354.
