Dimenhydrinate
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Dimenhydrinate, also known as diphenhydramine/8-chlorotheophylline salt and sold under the brand names Dramamine and Gravol, among others, is an over-the-counter medication used to treat
motion sickness Motion sickness occurs due to a difference between actual and expected motion. Symptoms commonly include nausea, vomiting, cold sweat, headache, dizziness, tiredness, loss of appetite, and increased salivation. Complications may rarely include ...
and
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
. Dimenhydrinate is a theoclate salt composed of
diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...
and 8-chlorotheophylline (a theophylline relative) in a 1:1 ratio. Dimenhydrinate was introduced to the market by G.D. Searle in 1949.


Medical uses

Dimenhydrinate is an over-the-counter (OTC) first-generation
antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...
indicated for the prevention and relief of nausea and vomiting from a number of causes, including motion-sickness and post-operative nausea.


Side effects

Common side effects of dimenhydrinate may include drowsiness, dry mouth, nose, or throat,
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
, 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.
Hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...
s,
psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...
, and an unusual sensitivity to sudden sounds have also been reported. Continuous and/or cumulative use of
anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...
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.


Pharmacology


Pharmacodynamics

Diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...
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 An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...
activity.


Pharmacokinetics

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


Recreational use

Dimenhydrinate is recreationally used as a
deliriant Deliriants are a subclass of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelics such as LSD and dissociatives such as ketamine, due to their primary effect of causing delirium, as opposed to th ...
. 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 amount of Dramamine tablets generally necessary for a recreational dose. Many users report a side-effect profile consistent with tropane alkaloid (e.g.
atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...
) poisoning as both show antagonism of
muscarinic acetylcholine receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...
s in both the central and autonomic nervous system, which inhibits various signal transduction pathways. Other CNS effects occur within the
limbic system The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''P ...
and
hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
, causing confusion and temporary
amnesia Amnesia is a deficit in memory caused by brain damage or brain diseases,Gazzaniga, M., Ivry, R., & Mangun, G. (2009) Cognitive Neuroscience: The biology of the mind. New York: W.W. Norton & Company. but it can also be temporarily caused by t ...
due to decreased
acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
signaling. Toxicology also manifests in the autonomic nervous system, primarily at the
neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...
, resulting in
ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...
and extrapyramidal side effects and the feeling of heaviness in the legs, and at sympathetic post-ganglionic junctions, causing urinary retention, pupil dilation,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...
, irregular urination, and dry red skin caused by decreased exocrine gland secretions, and mucous membranes. Considerable overdosage can lead to
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
(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.


History

Dimenhydrinate (then known as Compound 1694) was being tested as a potential treatment for
hay fever Allergic rhinitis, of which the seasonal type is called hay fever, is a type of rhinitis, inflammation in the nose that occurs when the immune system overreacts to allergens in the air. It is classified as a Allergy, type I hypersensitivity re ...
and
hives Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and typically ...
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 10 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 New York Times'' (''NYT'') is an American daily newspaper based in New York City. ''The New York Times'' covers domestic, national, and international news, and publishes opinion pieces, investigative reports, and reviews. As one of ...
'', the '' Baltimore Sun'', and other national newspapers covered the discovery, and Dramamine was made available in drugstores later that year.


Brand names

Dimenhydrinate is marketed under many brand names:


Popular culture

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.


References


External links

* {{Authority control Antiemetics Combination drugs Deliriants H1 receptor antagonists M1 receptor antagonists M2 receptor antagonists M4 receptor antagonists M5 receptor antagonists Motion sickness Dimethylamino compounds