Abstract

Dimenoxadol is a synthetic opioid analgesic that is commonly prescribed for the relief of moderate to severe pain. It belongs to the class of organic compounds known as diphenylmethanes and is considered a narcotic. Despite sharing structural similarities with synthetic anticholinergics, Dimenoxadol exhibits analgesic and antitussive properties. Compared to morphine and promedol, Dimenoxadol has lower analgesic potency but offers the advantage of causing less respiratory depression and vagus nerve tone increase. In this article, provide a comprehensive overview of Dimenoxadol, including its general information, physico-chemical properties, pharmacology, prices, dosage, legal status, synthesis of 2-(dimethylamino)ethyl 2-ethoxy-2,2-diphenylacetate, conclusion, and bibliography. With its potential for managing moderate to severe pain and unique properties, Dimenoxadol is an important opioid analgesic that merits further attention in clinical practice and research.

General Information About Dimenoxadol [1-4]

Other synonyms names of Dimenoxadol are: 2-(dimethylamino)ethyl 2-ethoxy-2,2-diphenylacetate

IUPAC Name of Dimenoxadol: 2-(dimethylamino)ethyl 2-ethoxy-2,2-diphenylacetate

CAS numbers is 509-78-4

Related CAS is 2424-75-1 (hydrochloride)

Trade names are Dimenoxadole; Dimenoxadolum; Estocine (Salt/Mix)

Physico-Chemical Properties of Dimenoxadol [1-4]

• Molecular Formula C₂₀H₂₅NO₃
• Molar Weight 327.4 g/mol
• Boiling point 185 °C (6 Torr); 444.5±40.0 °C at 760 mmHg
• Flash Point: 222.6±27.3 °C
• Solubility: Soluble in water and alcohol; Water Solubility 194 mg/L at 25 °C; pH of 2% solution is 4.0-5.5.
• Color/Form: White crystalline powder. powder; tablets of 5, 15, 30, and 60 mg; 2% solution in ampoules of 2 ml.

Structural formula present on Figure 1.

General Information, Pharmacology, Prices, Dosage of Dimenoxadol. [4-8]

General Information

Dimenoxadol is a synthetic opioid analgesic that is commonly prescribed for the relief of moderate to severe pain. It is classified as a Schedule I controlled substance in the United States due to its high potential for abuse and strict regulation. Dimenoxadol shares structural similarities with synthetic anticholinergics and exhibits analgesic and antitussive properties. Although its analgesic potency is lower than morphine and promedol, it has the advantage of causing less respiratory depression and vagus nerve tone increase. Dimenoxadol also has moderate spasmolytic and anticholinergic effects, making it useful for pain associated with smooth muscle spasms. It can be used alone or in combination with neuroleptics for premedication and in the postoperative period. Dimenoxadol is also utilized for pain management in trauma, dental surgery preparation, and during childbirth, although it may be less effective for severe pain resulting from extensive traumatic injuries.

Pharmacology

Dimenoxadol acts as a potent opioid agonist, binding to opioid receptors in the central nervous system (CNS) to produce its analgesic effects. However, its mechanism of action goes beyond opioids, as it also interacts with other receptors in the brain and spinal cord. Metabolized in the liver and primarily excreted in urine, Dimenoxadol exhibits not only analgesic properties but also antitussive, spasmolytic, and M-cholinoblocking actions. By inhibiting the thalamic centers of pain perception and blocking the transmission of pain impulses to the cerebral cortex, Dimenoxadol exerts its analgesic effects. Its interaction with opioid receptors in subcortical brain structures further enhances its pharmacological profile. Moreover, Dimenoxadol effectively suppresses the central links of the cough reflex, making it a valuable option for treating cough associated with severe pain. One of the advantages of Dimenoxadol is its favorable safety profile. It does not impact the tone of the vagus nerve and does not cause constipation, making it a preferred choice for patients who require effective pain relief without undesirable side effects. Additionally, its high permeability across the blood-brain barrier and placental barrier underscores its unique pharmacokinetics.

Dosage

The dosage of dimenoxadol is typically determined by a healthcare provider and may vary depending on the individual patient’s condition, severity of pain, and other factors. Dimenoxadol is available in different formulations, such as tablets or capsules, and the recommended dosage may differ for each formulation. It should not be used in higher doses or more frequently than prescribed, as it can lead to serious health risks, including overdose and dependence. As an analgesic, it is administered orally to adults at a dose of 30-60 mg 2-3 times a day. Subcutaneously and intramuscularly, it is injected at a dose of 20-40 mg (1-2 mL of 2% solution) 2-3 times a day. In a hospital setting, a single oral dose can be increased to 80 mg, and parenterally up to 60 mg (3 mL of 2% solution). The dose for children is reduced according to age. The analgesic effect occurs rapidly (within 10-15 minutes after injection and 20-30 minutes after oral administration) and is relatively short-lived (1-2 hours). As an antitussive, Estocin is used for respiratory and lung diseases accompanied by cough, including bronchospasm. It is prescribed orally to adults at a dose of 15 mg 2-3 times a day; for children over 2 years old, the dose is 5-10 mg depending on age. Estocin is not prescribed for children under 2 years of age. Estocin is generally well tolerated. Prolonged use may lead to tolerance and addiction. It is available with the same restrictions as other narcotic analgesics.

Effects, Symptoms, Dangerous Interactions of Dimenoxadol Use [4-8]

As a synthetic opioid analgesic, dimenoxadol can cause a range of effects and symptoms when used. Uncontrolled or improper use of dimenoxadol can have serious consequences and lead to undesirable effects, including:

• Opioid effects: Like other opioids, dimenoxadol can cause general effects such as sedation, decreased alertness, respiratory depression, and decreased heart rate.
• Central Nervous System (CNS) side effects: The use of dimenoxadol may cause various CNS side effects, such as dizziness, drowsiness, headache, coordination disturbances, and memory impairment.
• Gastrointestinal disturbances: Dimenoxadol may cause gastrointestinal side effects, including nausea, vomiting, constipation, or diarrhea.
• Allergic reactions: Like other medications, dimenoxadol may cause allergic reactions in some people, such as skin rashes, itching, facial, throat or tongue swelling, difficulty breathing, and rare but serious anaphylactic shock.
• Dependency and drug abuse: Dimenoxadol, like other opioids, can cause physical and psychological dependence in patients, especially with improper use or prolonged use. Drug abuse of dimenoxadol can also have serious consequences, including the development of addiction.
• Interactions with other medications: Dimenoxadol may interact with other medications, particularly other central nervous system (CNS) depressants such as sedatives, antidepressants, antihistamines, and other opioids.

Pharmacology – OPIOIDS (MADE EASY)

Legal Status

Dimenoxadol falls under the category of substances classified as Schedule I by the Drug Enforcement Administration (DEA) in the United States, which means it is considered to have no currently accepted medical use, a lack of accepted safety for use under medical supervision, and a high potential for abuse. As such, Dimenoxadol is tightly regulated, and its use is subject to strict restrictions, including the requirement of a prescription from a qualified physician. Furthermore, Dimenoxadol is classified as a Prohibited Substance (S9) in Australia, as Schedule I in Canada, as Anlage I (Authorized scientific use only) in Germany, and as a Psychotropic Schedule I substance by the United Nations. These international classifications further highlight the stringent regulations and controls in place for Dimenoxadol due to its high potential for abuse.

Synthesis of Dimenoxadol [9]

Dimenoxadol belongs to the class of organic compounds called diphenylmethanes. These compounds contain a diphenylmethane moiety, which is characterized by a methane molecule with two hydrogen atoms replaced by two phenyl groups. The synthesis of dimenoxadol begins with the preparation of the sodium or potassium salt of benzilic acid. This salt is then reacted with 2-(dimethylamino)-ethyl chloride to form the benzilic acid ester. The benzilic acid ester is further reacted with thionyl chloride (SOCl2) to yield diphenylchloroacetic acid 2-(dimethylamino)-ethyl ester hydrochloride. Next, diphenylchloroacetic acid 2-(dimethylamino)-ethyl ester hydrochloride is dissolved in absolute ethanol and stirred with calcium carbonate under reflux for 24 hours. The salts are filtered, and the solvent is evaporated in vacuum. The residue is then partitioned between sodium carbonate and ether. The etheral solution is decolorized with activated carbon, filtered, and extracted with 2N HCl until the extracts become clearly acidic. The water is evaporated in vacuum, and the residue is recrystallized from ethanol to obtain 70% of dimenoxadol hydrochloride, with a melting point of 166-167°C. This synthesis process is illustrated in Figure 4 according to the scheme outlined above.

Conclusion

Dimenoxadol is a synthetic opioid analgesic with potent pain-relieving properties, making it a commonly prescribed medication for the management of moderate to severe pain. However, it is classified as a narcotic and is tightly regulated due to its high potential for abuse. In fact, it is listed in the DEA Schedule I, which means it has no currently accepted medical use in the United States, lacks accepted safety for use under medical supervision, and poses a significant risk for abuse. As with other opioids, dimenoxadol can cause a range of effects and symptoms when used, including pain relief, sedation, respiratory depression, and euphoria. However, it also carries risks of adverse effects and complications, especially when used in an uncontrolled or improper manner.

Bibliography

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9. https://www.erowid.org/archive/rhodium/chemistry/dimenoxadol.html