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ARCHIVE:  July 9, 2003

DXM (Dextromethorphan)

Dear Dr. Shulgin:

Could you explain how DXM is synthesized? I have not been able to find any description anywhere. Not that I'd really try to synthesize it, but it would be a nice addition to my web site. -- Void

Dear Void:

DXM is the common abbreviation for Dextromethorphan. In small doses this is a remarkably effective cough suppressant, equivalent to small amounts of codeine without the associated analgesia and sedation. And at larger doses it has become broadly popular as a means for altering one's consciousness.

DXM is legally considered a synthetic opiate. It has been synthesized from a benzylisoquinoline (with a planar structure) by a process known as Grewe's cyclization (from the 1950's !) to give the corresponding morphinan (with a three dimensional structure). The isoquinoline is 1,2,3,4,5,6,7,8-octahydro-1-(4-methoxybenzyl)isoquinoline (there is just one residual double bond at the fusion position of the two rings of the isoquinoline) is converted into the N-formyl derivative, cyclized to the N- formyl normorphinan, and the formyl group reduced to an N-methyl group, to give 3-methoxy-17-methylmorphinan, or Racemethorphan.

This is a mixture of equal amounts of the (+)-isomer (Dextromethorphan) and the (-)-isomer (Levomethorphan) and this must be resolved into its two separate isomers. The racemic mixture (Racemethorphan) and the (-)-isomer (Levomethorphan) are both Schedule II drugs under the Controlled Substances Act, but the (+)-isomer (Dextromethorphan) has been exempted from scheduling (see 21 U.S.C. 812 (g)(2)). If an appropriate optical isomer of the octahydroisoquinoline is used, the illegal intermediate can be avoided.

Dextromethorphan (as the cough syrup) is easily available as an over the counter medication. But it is usually diluted with a number of other drugs. There can be expectorants present (such as guaifenesin), sympathomimetic agents (usually phenylephrine or ephedrine) and/or an antihistamine. And there can be sodium citrate and alcohol present. Obviously, if the dose of the OTC product taken for a trip is twenty times that which is recommended for a cough, the dose taken of any additional product goes up proportionally. My first exploration of this world was about 40 years ago, with a rather large number of Romular Capsules. I did not particularly enjoy it, and I never repeated it.

-- Dr. Shulgin

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