Diphenhydramine hydrochloride (trade name Benadryl®, as produced by Pfizer or Dimedrol outside the US) is an over-the-counter (OTC) antihistamine and sedative. It is also given in conjunction with typical antipsychotics to prevent akathisia. It is a member of the ethanolamine class of antihistaminergic agents.
Diphenhydramine is widely used in nonprescription sleep aids with a 50mg recommended dose mandated by the FDA. In the United Kingdom, Australia, New Zealand, South Africa, and other countries, a 50 to 100mg recommended dose is permitted. In spite of its use and effectiveness as a sleep-inducing agent, when this drug is sold as an antihistamine, warning of the potential loss of alertness is rarely prominently displayed on packaging.
Diphenhydramine works by blocking the effect of histamine at H1 receptor sites. This results in effects such as the reduction of smooth muscle contraction, making diphenhydramine a popular choice for treatment of the symptoms of allergic rhinitis, hives, motion sickness, and insect bites and stings.
Diphenhydramine is a first generation antihistamine drug. 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 nearpoint 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.
It is known that diphenhydramine contains sedative properties. Many new antihistamines have been introduced without the side effect of sedation. The drug is also used as a sleep aid and is an ingredient in many sleep aids, most notably Tylenol PM. No physical addictive properties have been noted to this day.
In the 1960s it was found that diphenhydramine inhibits reuptake of the neurotransmitter serotonin. This discovery led to a search for viable antidepressants with similar structures and fewer side effects, culminating in the invention of fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI). A similar search had previously led to the synthesis of the first SSRI zimelidine from chlorpheniramine, also an antihistamine.
It should be noted that taking any medication that depresses the Central Nervous system is not recommended before driving or operating heavy machinery, due to impaired reaction time.
The most common cardiac dysrhythmias associated with diphenhydramine overdose are sinus bradycardia, elongated S-T segment interval, and premature ventricular contraction.
Diphenhydramine is very similar in its effects to dimenhydrinate (Dramamine®), its 8-chlorotheophyllinate salt, although the latter is approximately 60% the potency in terms of required dosage and is slightly less sedating.
The brand Benadryl is currently trademarked in the United States by Pfizer, but many drug store chains and retail outlets manufacture substantially less expensive generic versions under their own store brands, often sold in boxes that share the size, shape and familiar pink packaging and pill color of the original.