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)[10] and the fact that the stimulant properties of 8-chloro­theo­phylline help reduce the side effect of drowsiness brought on by diphen­hydramine.

[16] 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.

Toxicology also 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.

[18] Dimenhydrinate (then 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.

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 10 days as a rescue therapy for sea sickness.

[3][4][19] Dimenhydrinate is marketed under many brand names: in the U.S., Mexico, Turkey and Thailand as Dramamine; in Serbia as Dimigal; in Ukraine as Driminate; in Canada, Costa Rica, and India as Gravol; in Iceland as Gravamin; in Russia and Croatia as Dramina; in South Africa and Germany as Vomex; in Australia as Travacalm; in Austria as Vertirosan; in Brazil as Dramin; in Colombia as Mareol; in Ecuador as Anautin; in Hungary as Daedalon; in Indonesia as Antimo; in Italy as Xamamina or Valontan; in Peru as Gravicoll; in Poland and Slovakia as Aviomarin;[20] in Portugal as Viabom, Vomidrine, and Enjomin; in Spain as Biodramina; in Israel as Travamin; and in Pakistan as Gravinate.