Dimenhydrinate
From Wikipedia, the free encyclopedia
 |
|
|
Dimenhydrinate
|
|
| Systematic (IUPAC) name | |
| 2-benzhydryloxy-N,N-dimethyl-ethanamine; 8-chloro-1,3-dimethyl-7H-purine-2,6-dione | |
| Identifiers | |
| CAS number | |
| ATC code | R06 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C24H28ClN5O3 |
| Mol. mass | 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.
[edit] 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 hallucinogenic dose starts around 900mg, (18 tablets of the original formula Dramamine). 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. Also, people commonly experience a sense of their body being unusually 'heavy,' especially in the legs, so much as to the point where they can't even walk, or where they constantly bump into things due to lack of control of their limbs. People commonly think that they are in a completely different environment, and not even realize it, this makes the drug especially dangerous. 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. Users also report extreme short-term amnesia, wearing off as the physical effects do.
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 dilation, tachycardia, and dry skin & mucous membranes. Considerable over dosage 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.
[edit] Veterinary Use
Dimenhydrinate has successfully been used as an antiemetic and sedative in housepets. It is commonly used to reduce the effects of idiopathic vestibular syndrome. The suggested dosage is 50 mg for dogs and 10 mg for cats; duration of effect is 8 hours.
[edit] Categorization
3-quinuclidinyl benzilate, Atropine, Dimenhydrinate, Diphenhydramine, Hyoscyamine, Scopolamine, Cyclizine
