Combination of | |
---|---|
Diphenhydramine | Antihistamine, sedative |
8-chlorotheophylline | Stimulant |
Clinical data | |
Trade names | Dramamine, Draminate, Gravol, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a607046 |
License data | |
Pregnancy category |
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Routes of administration | By mouth, rectal, intravascular, intramuscular |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Metabolism | Liver |
Elimination half-life | 5.5 hours [1] (diphenhydramine component) |
Identifiers | |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.007.593 |
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Dimenhydrinate, sold under the brand name Dramamine, among others, is an over-the-counter medication used to treat motion sickness and nausea. Dimenhydrinate is a theoclate salt composed of diphenhydramine (an ethanolamine derivative) and 8-chlorotheophylline (a chlorinated theophylline derivative) in a 1:1 ratio. [2]
Dimenhydrinate was introduced to the market by G.D. Searle in 1949. [3] [4]
Dimenhydrinate is an over-the-counter (OTC) antihistamine indicated for the prevention and relief of nausea and vomiting from a number of causes, including motion-sickness and post-operative nausea. [2]
Common side effects may include: [5]
Continuous and/or cumulative use of anticholinergic medications, including first-generation antihistamines, is associated with higher risk of cognitive decline and dementia in older people. [6] [7]
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) [8] 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. [9]
The diphenhydramine component requires about 2 hours to reach peak concentration after either oral or sublingual administration of diphenhydrinate, and has a half-life of 5 – 6 hours in healthy adults. [1]
Dimenhydrinate is recreationally used as a deliriant. [10] [11] [12] Slang terms for Dramamine used this way include "drama", "dime", "dime tabs", "D-Q", "substance D", "d-house", and "drams". [13] 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 trip. [14]
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. [11]
Other CNS effects occur within the limbic system and hippocampus, causing confusion and temporary amnesia due to decreased acetylcholine signaling. 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. Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular arrhythmias, coma, and death. [15] Such a side effect profile is thought to give ethanolamine-class antihistamines a relatively low abuse liability.[ citation needed ] An antidote that can be used for dimenhydrinate poisoning is physostigmine. [16]
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. 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 Baltimore Sun, and other national newspapers covered the discovery, and Dramamine was made available in drugstores later that year. [3] [4] [17]
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 and 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; [18] in Portugal as Viabom, Vomidrine, and Enjomin; in Spain as Biodramina; in Israel as Travamin; and in Pakistan as Gravinate. [19]
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. [20]
Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is used as a medication to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva. When used by injection, effects begin after about 20 minutes and last for up to 8 hours. It may also be used orally and as a transdermal patch since it has been long known to have transdermal bioavailability.
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 dehydration, electrolyte problems, or a lower esophageal tear.
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer. They may be used for severe cases of gastroenteritis, especially if the patient is dehydrated.
H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.
Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea. It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.
Anticholinergics are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.
Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the post-anesthesia care unit (PACU) or within 24 hours following a surgical procedure. PONV affects about 10% of the population undergoing general anaesthesia each year. PONV can be unpleasant and lead to a delay in mobilization and food, fluid, and medication intake following surgery.
Promethazine, sold under the brand name Phenergan among others, is a first-generation antihistamine, antipsychotic, sedative, and antiemetic used to treat allergies, insomnia, and nausea. It may also help with some symptoms associated with the common cold and may also be used for sedating people who are agitated or anxious, an effect that has led to some recreational use. Promethazine is taken by mouth (oral), as a rectal suppository, or by injection into a muscle (IM).
Doxylamine, sold under the brand name Unisom among others, is an antihistamine medication which is used in the treatment of insomnia and allergies. It is also used to treat morning sickness in pregnant women in combination with pyridoxine (vitamin B6). Doxylamine is available over-the-counter, and is used in nighttime cold medicines, such as NyQuil, as well as in pain medications containing acetaminophen and codeine, to help with sleep. The medication is taken by mouth.
A fasciculation, or muscle twitch, is a spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers. They are common, with as many as 70% of people experiencing them. They can be benign, or associated with more serious conditions. When no cause or pathology is identified, they are diagnosed as benign fasciculation syndrome.
Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.
Cyclizine, sold under a number of brand names, is a medication used to treat and prevent nausea, vomiting and dizziness due to motion sickness or vertigo. It may also be used for nausea after general anaesthesia or that which developed from opioid use. It is taken by mouth, in the rectum, or injected into a vein.
Tripelennamine, sold under the brand name Pyribenzamine by Novartis, is a drug that is used as an antipruritic and first-generation antihistamine. It can be used in the treatment of asthma, hay fever, rhinitis, and urticaria, but is now less common as it has been replaced by newer antihistamines. The drug was patented at CIBA, which merged with Geigy into Ciba-Geigy, and eventually becoming Novartis.
A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for an FDC product, although the latter is more precise if in fact referring to a mass-produced product having a predetermined combination of drugs and respective dosages. And it should also be distinguished from the term "combination product" in medical contexts, which without further specification can refer to products that combine different types of medical products—such as device/drug combinations as opposed to drug/drug combinations. When a combination drug product is a "pill", then it may also be a kind of "polypill" or combopill.
8-Chlorotheophylline, also known as 1,3-dimethyl-8-chloroxanthine, is a stimulant drug of the xanthine chemical class, with physiological effects similar to caffeine. Its main use is in combination (salt) with diphenhydramine in the antiemetic dimenhydrinate (Dramamine). Diphenhydramine reduces nausea but causes drowsiness, and the stimulant properties of 8-Chlorotheophylline help reduce that side effect.
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic drug that can be bought without a prescription and provides relief from nasal congestion, sneezing, or hives caused by pollen, dust mites, or animal allergy with few side effects. Antihistamines are usually for short-term treatment. Chronic allergies increase the risk of health problems which antihistamines might not treat, including asthma, sinusitis, and lower respiratory tract infection. Consultation of a medical professional is recommended for those who intend to take antihistamines for longer-term use.
Etanautine, also known as diphenhydramine monoacefyllinate, is an anticholinergic used as an antiparkinsonian agent. It is a 1:1 salt of diphenhydramine with acefylline, similar to the diphenhydramine/8-chlorotheophylline combination product dimenhydrinate.
Bromazine, sold under the brand names Ambodryl, Ambrodil, and Deserol among others, also known as bromodiphenhydramine, is an antihistamine and anticholinergic medication of the ethanolamine class. It is an analogue of diphenhydramine with a bromine substitution on one of the phenyl rings.
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.
Meclizine, sold under the brand name Bonine, among others, is an antihistamine used to treat motion sickness and dizziness (vertigo). It is taken by mouth. Effects generally begin in an hour and last for up to a day.