Diphenhydramine

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Image:Diphenhydramine Structure.png Diphenhydramine
IUPAC chemical name 2-(Diphenylmethoxy) -N,N-dimethylethylamine hydrochloride.
CAS number 147-24-0	ATC code  ?
Chemical formula	C17H21NO · HCl
Molecular weight	291.82 g/mol
Bioavailability	86% bound to plasma protein
Metabolism	Various cytochrome P450 liver enzymes
Elimination half-life	Approx. 6-8 hours in adults, 4-6 in children
Excretion	94% through the urine, 6% through feces
Pregnancy category	Class C
Legal status	Over-the-counter, non-regulated
Routes of administration	Oral, parenteral (IM), suppository

Indicated for: Antihistaminic Motion sickness Sedative Tardive dyskinesia Other uses: Halting allergic reactions, controlling extra-pyramidal side-effects induced by anticonvulsants

Contraindications: Use in neonates and premature infants Use in nursing mothers Use as a local anesthetic Use in people with hypersensitivity to diphenhydramine hydrochloride and other antihistamines of similar chemical structure

Non-medical use/abuse: Used as a hallucinogen/deliriant. Has a relatively low abuse-liability.

Side effects: Severe: Myocardial infarction, serious ventricular dysrhythmias, coma and death Atypical sensations: Feelings of heaviness, hearing disturbances Cardiovascular: Hypertension in sensitive individuals Ear, nose, and throat: Dryness of the nose and throat Endocrinal: Increased appetite Eye: Dryness of the eyes Gastrointestinal: Urinary retention, constipation Hematological: Hepatoxicity in extremely large dosages Musculoskeletal: Incoordination, slow muscle response, twitching, restlessness, extrapyramidal side-effects Neurological: Somnolence, confusion, clouded thinking, drowsiness, hallucinations, delirium Psychological: Agitation, emotional lability, depression, excitability (especially in children) Respiratory: Few Skin: Phytosensitivity, flushing Urogenital and reproductive: Sexual disfunction, vaginal dryness, decreased libido Miscellaneous: ?

Diphenhydramine hydrochloride (trade name Benadryl^®, 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 tardive dyskinesia. It is a member of the ethanolamine class of antihistaminergic agents.

Diphenhydramine is widely used in nonprescription sleep aids (Nytol, Sominex, Unisom, Compoz, Excedrin PM, etc.) 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 recomended dose is permitted.

Unlike true antihistamines, which prevent the release of histamine, 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, the drug is the most deferred to when an allergic reaction requires a strong and quick 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, and delirium.

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.

Recreational drug users sometimes take several times the recommended dose of diphenhydramine in order to attain an intense hallucinogenic (more accurately, delirious) state. The mental effects are described by many as "dreaming while awake" involving visual and auditory hallucinations which, unlike those experienced with most psychedelics, often cannot be readily distinguished from reality. Many users report a side effect profile consistent with tropane glycoalkaloidal poisoning. This is due to antagonism of muscarinic acetylcholine receptors in both the central and autonomic nervous system, inhibiting various signal transduction pathways. In the CNS, diphenhydramine readily crosses the blood-brain barrier, exerting effects within the visual and auditory cortex, accounting for reported visual and auditory disturbances. Other CNS effects occur within the limbic system and hippocampus, causing confusion and temporary amnesia. Toxicology also manifests in the autonomic nervous system, primarily at the neuromuscular junction, resulting in ataxia and extrapyramidal side-effects, and at sympathetic post-ganglionic junctions, causing urinary retention, pupil dialation, tachycardia, and dry skin & mucous membranes. Considerable overdosage can lead to myocardial infarction, serious ventricular dysrhythmias, coma and death. Such a side-effect profile is thought to give ethanolamine-class antihistamines a relatively low abuse liability.

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.

External links

• Dimenhydrinate FAQ - Information on use as a recreational drug.
• Prescription Information (PDF)
• SSRI Withdrawal Procedure

References

• Bruce G. Charlton, Self-managment of psychiatric symptoms using over-the-counter (OTC) psychopharmacology: the S-DTM therapeutic model - self-diagnosis, self-treatment, self-monitoring. Medical Hypotheses 2005; 65: 823-828.
• J.A. Lieberman, History of the use of antidepressants in primary care. Primary Care Companion, Journal of Clinical Psychiatry 2003; 5 (supplement 7).