Dimethoxanate (trade names Cothera, Cotrane, Atuss, Perlatoss, Tossizid) is a

cough suppressant Cold medicines are a group of medicinal, medications taken individually or in Combination drug, combination as a Symptomatic treatment, treatment for the symptoms of the common cold and similar conditions of the upper respiratory tract. The ter ...

of the

phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. ...

class.

Side effects

Dimethoxanate may have

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

local anesthetic A local anesthetic (LA) is a medication that causes absence of all sensation (including pain) in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensati ...

, and

central nervous system depressant Depressants, also known as central nervous system depressants, or colloquially known as "downers", are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various are ...

effects, but it may also produce nausea and vomiting.

Pharmacology

It binds to the

sigma-1 receptor The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a Chaperone (protein), chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by ...

in the brain with an IC₅₀ of 41 nM.

Society and culture

Dimethoxanate was introduced in Austria, Belgium, and France in 1911, and in Italy and Spain in 1963. Approval for marketing in the US was withdrawn by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

in 1975 due to lack of evidence of efficacy.

Synthesis

Phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. ...

(1) is reacted with

phosgene Phosgene is an organic chemical compound with the formula . It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. It can be thought of chemically as the double acyl chloride analog of ...

to give Phenothiazine-10-carbonyl chloride 8956-87-1(2). Further reaction with 2-(2-(dimethylamino)ethoxy)ethanol 704-62-7(3) completed the synthesis of Dimethoxanate (4).

References

{{Sigma receptor modulators Phenothiazines Antitussives Sigma agonists Carbamates Ethers Dimethylamino compounds Ethanolamines Abandoned drugs Withdrawn drugs