API: Diphenhydramine

What Is Diphenhydramine and How Does It Work?

Diphenhydramine is a first generation antihistamine commonly used for allergy relief. It belongs to the ethanolamine class of antihistamines, and it works as an inverse agonist on the histamine-1 (H1) receptor. By competitively inhibiting the H1 receptor, diphenhydramine reduces the effects of endogenous histamine on bronchial, capillary, and gastrointestinal smooth muscles.The drug also blocks intracellular sodium channels, producing local anesthetic effects. In addition, it has anticholinergic effects that result from the drug’s ability to act as a competitive antagonist on muscarinic acetylcholine receptors in the brain.1

Approved Indications2:

  • Allergies and Hay Fever: Diphenhydramine can be used to treat the symptoms of allergies and hay fever, including runny nose, watery or itchy eyes, cough, sore throat, and rash.
  • Common Cold: Diphenhydramine treats the above symptoms when they are caused by the common cold.
  • Insomnia: Diphenhydramine can act as a sedative, making it easier for patients suffering from insomnia to fall asleep.
  • Motion Sickness: Diphenhydramine can reduce nausea, vomiting, and dizziness caused by motion sickness.
  • Parkinson’s Disease: Because of its anticholinergic properties, diphenhydramine can be used to treat symptoms of Parkinson’s disease, including shaking and muscle stiffness.
  • Skin Reactions: When applied topically, diphenhydramine can reduce pain and itching caused by insect bites, minor cuts and burns, and rashes from poison ivy, poison oak, and poison sumac.

Side Effects and Drug Interactions:

Common side effects of diphenhydramine include:

  • Drowsiness
  • Dizziness or loss of coordination
  • Upset stomach or constipation
  • Dry mouth, nose, or throat
  • Blurred vision

Patients should contact a doctor immediately if they experience these less common but serious side effects:  

  • Difficulty urinating
  • Irregular heartbeat
  • Abrupt mental or mood changes (especially restlessness or confusion)
  • Seizures
  • Severe allergic reaction

Women who are breastfeeding should not take diphenhydramine. It’s crucial to talk to a doctor before using diphenhydramine if a patient has liver or kidney disease, asthma or COPD, heart disease, glaucoma, or a thyroid disorder. The drug is not recommended for patients older than sixty, as older patients may be particularly susceptible to the sedative side effects of diphenhydramine.

Patients should talk to a doctor before using diphenhydramine in conjunction with potassium, sleeping pills, narcotic pain medications, muscle relaxants, or medicines for anxiety, depression, or seizures. Alcohol use may also enhance the sedative effects of the drug.3

Latest News and Research

Diphenhydramine was first synthesized at the University of Cincinnati in the early 1940’s and approved by the FDA in 1946 as the prescription drug Benadryl. In the 1980’s, the drug was approved for over-the counter-use.4

The latest research on diphenhydramine suggests that long-term use may have negative effects on cognitive functioning. These studies show that diphenhydramine and other anticholinergics are associated with an increased risk of dementia5, and brain scans suggest that using the drug can reduce brain size and lower metabolism.6

In addition to its antihistamine, anesthetic, and anticholinergic actions, diphenhydramine may also act as a serotonin reuptake inhibitor (SSRI), so it could have antidepressant effects.7 The drug’s ability to induce sleep may also be able to reduce the risk of postpartum depression by improving the quality of sleep during pregnancy.8

Although diphenhydramine is available over-the-counter in the United States, it is a prohibited substance in the Republic of Zambia. Several American travelers have been charged with drug-trafficking and jailed by the Zambian Drug Enforcement Commission for possession of drugs that contain diphenhydramine, such as Benadryl.9

Buying Guide

Many compound pharmacists prefer Levocetirizine, which provides allergy relief without sedative side effects. Please find more information about our Bulk APIs here.

Show 9 footnotes

  1. “Diphenhydramine,” 2016, https://pubchem.ncbi.nlm.nih.gov/compound/diphenhydramine#section=Top
  2. “Diphenhydramine,” March 1, 2016, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0000586/
  3. “Diphenhydramine,” November 19, 2013, http://www.drugs.com/diphenhydramine.html
  4. “George Rieveschl; invented Benadryl,” September 30, 2007, http://archive.boston.com/news/globe/obituaries/articles/2007/09/30/george_rieveschl_invented_benadryl/
  5. “Common anticholinergic drugs like Benadryl linked to increased dementia risk,” September 10, 2015, http://www.health.harvard.edu/blog/common-anticholinergic-drugs-like-benadryl-linked-increased-dementia-risk-201501287667
  6. “Brain scans link physical changes to cognitive risks of widely used class of drugs,” April 18, 2016, https://www.sciencedaily.com/releases/2016/04/160418120100.htm
  7. “Serotonin Reuptake Inhibition by Diphenhydramine and Concomitant Linezolid Use Can Result in Serotonin Syndrome,” October 2008, http://journal.publications.chestnet.org/article.aspx?articleid=1094281
  8. “Sleep Interventions During Pregnancy Reduce the Risk of Postpartum Depression,” April 16, 2014, https://womensmentalhealth.org/posts/sleep-interventions-pregnancy-reduce-risk-postpartum-depression/
  9. “Criminal Penalties in Zambia,” 2016, http://www.countryreports.org/travel/Zambia/criminalpenalties.htm