Chemical properties
Dextromethorphan, what is it? This chemical compound is an antitussive, an optical levorotatory isomer of methorphan. Despite its similarity to morphine , the drug does not have opiate effects.
Typically, the substance is found in drugs in the form of dextromethorphan hydrobromide . These are white crystals, bitter in taste, without a specific odor. Molecular weight of the compound = 370.3 grams per mole. It dissolves well in chloroform , less so in water and ether . One of the main ways to obtain Dextromethorphan is by methylation of 3-hydroxy-N-methylmorphinan .
The substance is most often used in combination with other medications as a substitute for codeine . a dissociative is also widespread . Also in medicine, the drug is used for diagnostics and treatment of seizures, alcoholism, some neurodegenerative diseases and heroin addiction. Sometimes the medicine is used to treat mental retardation in children, Parkinson's disease , lung cancer and transplantation.
Due to the fact that dextromethorphan in high dosages can have an effect similar to dissociative and psychedelic substances (similar to phencyclidine and ketamine ), it is used for recreational purposes . The substance may cause psychological dependence.
Research is also being conducted on the drug's ability to block NMDA channels in pancreatic cells and lead to blocking the increase in basal insulin . This property can be used to help patients diabetes who were previously forced to take metformin . Perhaps the drug is able to increase the intensity of insulin production without leading to negative consequences, namely hypoglycemia .
On the territory of the Russian Federation, this chemical compound is included in the 3rd list of narcotic drugs, the circulation of which is limited by the state. Most often, the medicine can be seen in cough syrups, oral capsules or tablets.
Duration
Dextromethorphan is available in the form of tablets, pills, syrups and is consumed by mouth.
Rarely, tablets are crushed and dissolved in liquid. In small doses, the drug has an antitussive effect that lasts up to 5 hours. At higher doses it causes dissociation, which lasts up to 8 hours after ingestion. In low doses (about 1.5-2.5 mg per kg of body weight), the drug has a weak stimulating effect: it enhances the pleasant sensations from music or movements. As the dose increases, a psychotropic effect similar to the use of nitrous oxide or marijuana is possible. Due to short-term memory impairments, mild hallucinations sometimes occur.
At a dose of about 7.5-15 mg per kg of body weight, hallucinations, disturbances in thinking, sensory perception of the environment and memory are possible. At doses greater than 15 mg/kg body weight, the effect is similar to a non-anesthetic dose of ketamine, which causes severe dissociation.
At a dose of 20-30 mg/kg body weight, dextromethorphan is toxic to the body - this does not mean that poisoning cannot occur even at lower doses. The drug is not a “dance drug”: the effect is incomparable to “ecstasy” in terms of euphoria and with ketamine in terms of dissociation.
Dextromethorphan is primarily used by adolescents as a recreational psychotropic drug. The most commonly used dosage at rave parties is up to 120 mg, at which euphoria, hallucinations and dissociation occur. Less commonly used is a dose of 120 mg, which is characterized by an “out-of-body” experience.
Pharmacodynamics and pharmacokinetics
Dextromethorphan hydrobromide, after penetration into the systemic bloodstream, acts directly on the cough center located in the medulla oblongata, reducing the center’s sensitivity threshold to external irritants and preventing dry cough . When used in therapeutic doses, the substance does not have analgesic , hypnotic or narcotic effects .
After oral administration, the medicine begins to act within 10 minutes to half an hour. The duration of action is from 5 to 9 hours (children). In the brain, the substance also affects the processes of serotonin and activates sigma receptors. The drug is capable of blocking N-methyl-D-aspartate channels when using dosages greater than 150 mg.
The absolute bioavailability of the product is 11%. Metabolism of the drug occurs in the liver tissues, with the participation of the cytochrome P450 (mainly CYP2D6 , less pronounced CYP3A4 and CYP3A5 ). Metabolites are removed from the blood plasma by the kidneys within 1.4 - 4 hours.
Pharmacological properties of the drug Dextromethorphan
A synthetic antitussive agent, similar in chemical structure to opiates (it is the methyl ether of the dextra isomer of levonorphanol, an analogue of codeine). The antitussive effect is not inferior to that of codeine and, like the latter, has a central effect, affecting the cough center and increasing the cough threshold. Dextromethorphan is also a low-affinity antagonist of N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptors involved in various processes in the central nervous system, including nociception. In therapeutic doses, dextromethorphan does not have an analgesic or sedative effect and does not cause respiratory depression. Does not affect mucociliary clearance. Quickly absorbed in the digestive tract. The antitussive effect develops 15–30 minutes after oral administration. Actively metabolized in the liver. The half-life is 11 hours, the antitussive effect lasts for 5–6 hours. It is excreted mainly by the kidneys in the form of metabolites and only a small amount is unchanged.
Interaction
When combining the drug with MAO inhibitors ( selegiline , furazolidone , procarbazine collapse , dizziness, adrenergic crisis , increased blood pressure, agitation, nausea, intracranial bleeding, tremor and spasms, up to lethargy and coma may occur .
The simultaneous use of the drug and tricyclic antidepressants is fraught with the development of serotonin syndrome and death.
Under the influence of agents that inhibit the cytochrome P450 ( quinidine , amiodarone , fluoxetine , etc.), the concentration of Dextromethorphan in the blood may increase and the time of its action on the body may be extended.
Inhalation of tobacco smoke leads to increased secretion of the glands, which is extremely undesirable given the suppression of the cough reflex that occurs under the influence of the drug.
Long-term consequences
The drug causes predominantly mental dependence. Dizziness, high blood pressure, nausea and headache occur within two weeks of taking higher doses.
Because dextromethorphan is never sold in its pure form, overdoses cause other unpleasant and long-term effects that depend on the substances added. Like all medicines, it is not recommended to combine the substance with other medicines, as serious side effects, including death, are possible.
Drugs containing (Analogs)
Level 4 ATC code matches:
Trigamma
Riluzole
Huato Boluses
Vitagamma
Vitaxon
Hypoxene
Glycine
Mexiprim
Mexidol
Neurox
Glitsed
Cytoflavin
The substance in combination with paracetamol is part of the drugs: Padevix , Grippostad Good Knight , Fervex for dry cough (+ ascorbic acid ), Grippex (+ pseudoephedrine ).
In combination with chlorphenamine , paracetamol and pseudoephedrine, the drug is found in the following medications: Tylenol for colds, Tylenol for children for colds, Mulsinex .
Dextromethorphan is also included in Toff Plus (+ paracetamol + chlorphenamine + phenylephrine Glycodin syrup (+ levomenthol + terpinhydrate ), Alex Plus , Caffetin Cold , Terasil-D , Tussin Plus ( guaifenesin ).
DEXTROMETHORPHAN
Pharmacological properties
Dextromethorphan is an antitussive agent. Dextromethorphan suppresses cough of any etiology, due to inhibition of the excitability of the cough center. Dextromethorphan does not have a hypnotic or analgesic effect, and does not cause addiction. The onset of action of dextromethorphan is observed 10–30 minutes after oral administration; its duration is 6–9 hours in children and 5–6 hours in adults. When taken orally, dextromethorphan is completely absorbed from the gastrointestinal tract. The maximum concentration of dextromethorphan in the blood serum is achieved after 2 hours. Dextromethorphan is biotransformed in the liver. About 45% of the drug is excreted by the kidneys, with significant individual variability in the excretion rates of individual metabolites.
Indications
Dry cough (of various origins).
Method of administration of dextromethorphan and dose
Dextromethorphan is taken orally, patients over 12 years old are prescribed 15 mg 4 times a day, patients over 6 years old 4 times a day 7.5 mg.
Contraindications for use
Hypersensitivity, bronchitis, bronchial asthma, combined use of mucolytic drugs, lactation period, pregnancy.
Restrictions on use
Violation of the functional state of the kidneys and/or liver.
Use during pregnancy and breastfeeding
The use of dextromethorphan is contraindicated during pregnancy. Breastfeeding should be discontinued during dextromethorphan therapy.
Side effects of dextromethorphan
Drowsiness, dizziness, nausea.
Interaction of dextromethorphan with other substances
Dextromethorphan enhances the effect of antitussive drugs and other drugs that depress the central nervous system. There is a potential reaction with monoamine oxidase inhibitors, so the combined use of dextromethorphan and monoamine oxidase inhibitors should be avoided.
Overdose
In case of an overdose of dextromethorphan, dizziness, agitation, respiratory depression, decreased blood pressure, impaired consciousness, tachycardia, ataxia, and muscle hypertonicity develop. Required: symptomatic treatment, artificial ventilation.
Trade names of drugs containing the active ingredient dextromethorphan
Combined drugs: Guaifenesin + Dextromethorphan: Tussin plus; Dextromethorphan + Paracetamol: Grippostad® Good Night, Padevix®; Dextromethorphan + Paracetamol + Ascorbic acid: Fervex for dry cough; Dextromethorphan + Paracetamol + Pseudoephedrine: Grippex®, Gripend; Dextromethorphan + Paracetamol + Pseudoephedrine + Chlorphenamine: Children's Tylenol™ Cold, Mulsinex, Tylenol™ Cold; Dextromethorphan + Paracetamol + Phenylephrine + Chlorphenamine: Toff plus; Dextromethorphan + Terpinhydrate + Levomenthol: Alex Plus, Glycodin; Dextromethorphan + Paracetamol + Pseudoephedrine + [Ascorbic acid]: Caffetin® Cold; Dextromethorphan + Phenylephrine + Chlorphenamine: Terasil-D
