Dimethoxanate Explained

Dimethoxanate (trade names Cothera, Cotrane, Atuss, Perlatoss, Tossizid)^[1] is a cough suppressant of the phenothiazine class.^[2]

Side effects

Dimethoxanate may have analgesic, local anesthetic, and central nervous system depressant effects, but it may also produce nausea and vomiting.^[3]

Pharmacology

It binds to the sigma-1 receptor in the brain with an IC₅₀ of 41 nM.^[4]

Society and culture

Dimethoxanate was introduced in Austria, Belgium, and France in 1911, and in Italy and Spain in 1963.^[5] Approval for marketing in the US was withdrawn by the FDA in 1975 due to lack of evidence of efficacy.^[6]

Synthesis

Phenothiazine (1) is reacted with phosgene to give Phenothiazine-10-carbonyl chloride [18956-87-1] (2). Further reaction with 2-(2-(dimethylamino)ethoxy)ethanol [1704-62-7] (3) completed the synthesis of Dimethoxanate (4).

Notes and References

1. Book: William Andrew Publishing . Pharmaceutical Manufacturing Encyclopedia . 22 October 2013 . Elsevier . 978-0-8155-1856-3 . 1332–3 .
2. Parish FA . Clinical evaluation of the antitussive, dimethoxanate . Medical Times . 87 . 1488–90 . November 1959 . 14430450 .
3. Book: 9788448604271. Farmacología clínica y terapéutica médica. Martín. Alfonso Velasco. 2004. Tratamiento sintomático de la tos y del resfriado común. 260. McGraw-Hill/Interamericana .
4. Klein M, Musacchio JM . Dextromethorphan binding sites in the guinea pig brain. . Cellular and Molecular Neurobiology . 8 . 2 . 149–156 . October 10, 1988 . 10.1007/BF00711241 . 3044591 . 33844132 .
5. Book: 0-8103-7177-4 . Drugs Available Abroad, 1st Edition . 67 . 1991 . Schlesser JL . Derwent Publications Ltd..
6. Cough Preparation Containing Dimethoxanate Hydrochloride. 75N–0321 . December 18, 1975 . Federal Register . 40 . 244 .