Article: Dimenhydrinate

Dimenhydrinate
Systematic (IUPAC) name
2-benzhydryloxy-N,N-dimethyl-ethanamine; 8-chloro-1,3-dimethyl-7H-purine-2,6-dione
Identifiers
CAS number	523-87-5
ATC code	R06AA02
PubChem	10660
DrugBank	APRD00924
Chemical data
Formula	C24H28N5ClO3
Mol. weight	469.964
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic (cytochrome P450)
Half life	1 - 4 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	B (U.S.)
Legal status	OTC) (U.S.)
Routes	Oral

Dimenhydrinate (marketed under brand names Dramamine and Gravol) is an over-the-counter drug used to prevent motion-sickness (emesis). It is closely related to diphenhydramine HCl, or Benadryl. The differences relate to the weight-for-weight potency (50mg dimenhydrinate contains 29mg of the drug diphenhydramine), delay of action (dimenhydrinate must dissociate into diphenhydramine and its counterion in the body before it is active, therefore diphenhydramine produces effects sooner), and degree of sedation produced. Chemically, dimenhydrinate is a salt of two drugs: diphenhydramine(+) and 8-chlorotheophyllinate(-). Chlorotheophyllinate is a chlorinated form of the drug theophylline. The chlorination provides the necessary charge to associate with diphenhydramine as a solid. Theophylline is very closely related to caffeine and theobromine, mild central nervous system stimulants. It was thought that by combining the antiemetic effects of diphenhydramine with a stimulant, the extreme drowsiness induced by the former could be mitigated somewhat by the latter. In actuality, the sedation caused by diphenhydramine is substantially stronger than the stimulation caused by chlorotheophyllinate. Diphenhydramine, an ethanolamine-class antihistamine, is found in most OTC sleep aids and allergy preparations, such as Tylenol PM and Benadryl. It is primarily a H₁-antagonist, but also possesses an antimuscarinic effect. It is used in Dramamine to prevent nausea and emesis, however the development of the chemical meclizine has overtaken its usage (marketed as "Dramamine II") due to the fact that meclizine doesn't produce as much drowsiness.

Recreational Use

Recreational drug users sometimes take several times the recommended dose of dimenhydrinate in order to attain an intense and long-lasting state of anticholinergic delirium.

For many, the minimum hallicinogenic dose starts around 30 pills. The mental effects are described by many as "dreaming while awake" involving visual and auditory hallucinations which, unlike those experienced with recreational drugs known as psychedelics, often cannot be readily distinguished from reality. Users often report a highly unpleasant side effect profile consistent with tropane glycoalkaloidal poisoning. This includes dry mouth and eyes, rapid heart beat (tachycardia), somnolence, insomnia, and extreme malaise. 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

Veterinary Use

Dimenhydrinate has successfully been used as an anti-emetic and sedative in housepets. The suggested dosage is 50 mg for dogs and 10 mg for cats; duration of effect is 8 hours.

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