Dimenhydrinate

Dimenhydrinate is an over-the-counter (OTC) first-generation antihistamine indicated for the prevention and relief of nausea and vomiting from a number of causes, including motion-sickness and post-operative nausea.

Common side effects of dimenhydrinate may include drowsiness, dry mouth, nose, or throat, constipation, and blurred vision. Some individuals, particularly children, may experience feelings of restlessness or excitement. In certain cases, more severe symptoms may arise, such as delirium, weakness, and a tendency to be easily startled. Hallucinations, psychosis, and an unusual sensitivity to sudden sounds have also been reported. Continuous or cumulative use of anticholinergic medications, including first-generation antihistamines, is associated with higher risk of cognitive decline and dementia in older people. However, in younger people this is not relevant.

Pharmacodynamics

Diphenhydramine is the primary constituent of dimen­hydrinate and dictates the primary effect. The main differences relative to pure diphen­hydramine are a lower potency due to being combined with 8-chloro­theo­phylline (by weight, dimen­hydrinate is between 53% and 55.5% diphen­hydramine) and the fact that the stimulant properties of 8-chloro­theo­phylline help reduce the side effect of drowsiness brought on by diphen­hydramine. Diphen­hydramine is itself an H₁ receptor antagonist that demonstrates anticholinergic activity.

Pharmacokinetics

The diphenhydramine component requires about 2 hours to reach peak concentration after either oral or sublingual administration of dimen­hydrinate, and has a half-life of 5 ,  6 hours in healthy adults.

Dimenhydrinate is recreationally used as a deliriant. Slang terms for Dramamine used this way include "drama", "dime", "dime tabs", "D-Q", "substance D", "d-house", and "drams". Abusing Dramamine is sometimes referred to as Dramatizing or "going a dime a dozen", a reference to the number of Dramamine tablets generally necessary for a recreational dose.

Many users report a side-effect profile consistent with tropane alkaloid (e.g., atropine) poisoning as both show antagonism of muscarinic acetylcholine receptors in both the central and autonomic nervous system, which inhibits various signal transduction pathways.

Other CNS effects occur within the limbic system and hippocampus, causing confusion and temporary amnesia due to decreased acetylcholine signaling. Toxicity manifests in the autonomic nervous system, primarily at the neuromuscular junction, resulting in ataxia and extrapyramidal side effects and the feeling of heaviness in the legs, and at sympathetic post-ganglionic junctions, causing urinary retention, pupil dilation, tachycardia, irregular urination, and dry red skin caused by decreased exocrine gland secretions, and mucous membranes. Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular arrhythmias, coma, and death. Such a side-effect profile is thought to give ethanolamine-class antihistamines a relatively low abuse liability. An antidote that can be used for dimenhydrinate poisoning is physostigmine.

Dimenhydrinate (originally known as Compound 1694) was being tested as a potential treatment for hay fever and hives at Johns Hopkins Hospital in 1947 by allergists Dr. Leslie Gay and Dr. Paul Carliner. Among those who received the drug was a pregnant woman who had suffered from motion sickness her entire life. She remained symptom-free if she took dimenhydrinate a few minutes before boarding a trolley, whereas the placebo was ineffective. To confirm these findings, the following year, G.D. Searle & Co. conducted a trial in which dimenhydrinate or placebo was given to U.S. troops crossing the Atlantic during "a rough passage" in a converted freight ship, the General Ballou, for ten days as a rescue therapy for sea sickness. The findings were positive, as were the findings of a second trial of mostly women on the ship's return voyage. Gay and Carliner announced their discovery at a meeting of the Johns Hopkins Medical Society on February 14, 1949, as well as in the Bulletin of The Johns Hopkins Hospital. The New York Times, the Baltimore Sun, and other national newspapers covered the discovery, and Dramamine was made available in drugstores later that year.

Dimenhydrinate is marketed under many brand names:

Modest Mouse produced a song titled "Dramamine" on their 1996 debut album This Is a Long Drive for Someone with Nothing to Think About. The song uses side effects of the drug as a metaphor for the deteriorating state of a personal relationship.

"The Ending of Dramamine" is the opening track of the album How to Leave Town by Car Seat Headrest.

Wallice's 2021 EP Off the Rails has a track titled "Dramamine" utilizing the motion sickness drug as a metaphor for navigating an emotionally taxing relationship.