Dextromethorphan

Dextromethorphan (DXM or DM) is an antitussive (cough suppressant) drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, including generics and proprietary brands such as Mucinex DM, Robitussin, NyQuil, Dimetapp, Vick, Bisolsek, Coricidin, Delsym, TheraFlu and others.

Dextromethorphan also has other uses in medicine, ranging from pain relief to psychiatric applications.

It is sold in syrups, tablets, powder and in rhomboid shapes. In its pure form, dextromethorphan is a white powder.

Chemistry

Dextromethorphan is the dextrorotatory enantiomer of levomethorphan, which is a methyl of levorphanol, both of which are opioid analgesics. It gets its name according to IUPAC as 3-methoxy-17-methyl-(9α,13α,14α)-morphinan. In its pure state dextromethorphan is odorless, yellowish white in a crystalline powder. It is soluble in chloroform and insoluble in water. Dextromethorphan is available as a hydrobromide salt, although newer extended-release formulations contain dextromethorphan bound to an ion exchange resin such as sodium polystyrene sulfonate.

The specific rotation in water is +27.6º.

Medical use

The main use of dextromethorphan is as a cough suppressant (cough suppressant), for the temporary relief of cough caused by minor bronchial irritation (such as that accompanying the common cold), and as a result of inhaling irritating particles. A 2004 study showed that in children, dextromethorphan was no more effective than a placebo. Studies by the American Academy of Pediatrics showed that dextromethorphan is not superior to a placebo in relieving nighttime symptoms for children with cough and difficulty sleeping due to upper and lower respiratory tract infections.

A combination of dextromethorphan and quinidine, a CYP2D6 inhibitor, has been shown to relieve symptoms of sudden episodes of laughing and crying (due to pseudobulbar involvement) in patients with amyotrophic lateral sclerosis and multiple sclerosis. In 2010, the FDA approved this combination of dextromethorphan and quinidine ('Nuedexta') for the treatment of pseudobulbar involvement.

It is also used to treat major depressive disorder, with another combination, this time of dextromethorphan and bupropion, the latter being an inhibitor of the CYP2D6 enzyme, thus allowing dextromethorphan to remain in the blood longer. It is marketed under the brand Auvelity™ and received FDA approval in August 2022.

Dextromethorphan is also being investigated as a possible treatment for neuropathic pain and pain associated with fibromyalgia.

Recreational use

Since its introduction, over-the-counter preparations containing dextromethorphan have been used in doses outside those specified as a recreational drug. At doses higher than those medically recommended, dextromethorphan is classified as a dissociative hallucinogen, having certain effects somewhat similar to dissociative hallucinogenic agents such as ketamine and phencyclidine. It can produce distortions of the visual field, sensations of dissociation, distortion of body and emotional perception as well as loss of notion of time. Many users have reported euphoric effects, particularly in response to music. Dextromethorphan usually provides its recreational effects in a non-linear manner, that is, being experienced in various stages. These five stages are commonly known as 'levels'.

Adverse effects

Side effects of dextromethorphan include:

In high doses:

• Urticaria
• Nausea
• Vertigo
• Mare
• Enclosing eyes closed
• Difficulty breathing

In very high doses, 360mg or higher:

• Alucinations
• Dissociation
• Vomit
• Blurred vision
• Red eyes
• Pupils dilated
• Sweating
• Fiber
• Hypertension
• Surface breathing
• Diarrhea
• Urinary detention
• Muscle spasms
• Sedation

Dextromethorphan can also cause gastrointestinal upset. It is also known to cause Olney lesions when administered intravenously, although this has been questioned due to the lack of evidence in humans, as it was tested in rats by administering 50mg each day for a month. Neurotoxic changes, including vacuolization, have been observed in the posterior cingulate and retrosplenial cortices of rats administered other NMDA antagonists such as PCP, but not dextromethorphan. In many documented cases, dextromethorphan has produced psychological dependence in people They have used it recreationally; In any case, it does not produce physical addiction, according to the drug dependence committee of the World Health Organization.

Contraindications

Because dextromethorphan can activate the release of histamine (allergic reaction), it should be administered to children who are susceptible to allergic reactions only if absolutely necessary, and with the strict supervision of a professional.

Interactions with other medications

Dextromethorphan should not be taken if you are under treatment with monoamine oxidase inhibitors, due to the possible appearance of serotonin syndrome, which is potentially dangerous and can occur quickly due to an excessive accumulation of serotonin in the body. Dextromethorphan can also cause serotonin syndrome when used with SSRI medications, but research has shown that this interaction only occurs if taken at recreational doses and not therapeutic doses.

There are users who report having used levomepromazine as an enhancer of the effects of dextromethorphan, when used recreationally, there have not been many studies done yet on whether using this combination of medications can increase the adverse effects.

Interactions with food

Some care should be taken when consuming dextromethorphan with grapefruit or grapefruit juice, because this fruit interacts with different medications such as dextromethorphan, by inhibiting the cytochrome p450 system in the liver and causing excessive accumulation, as well as longer-lasting effects.. It is generally recommended to avoid grapefruit consumption when taking dextromethorphan and other medications.

Laboratory tests

Laboratory tests for this medication can be done through blood or urine. For blood it can be serum or plasma, in serum preferably 2 milliliters, in urine at least 2 milliliters.