A New Way to Buffer Amphetamine For ADHD Treatment

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Mark Dombeck, Ph.D. was Director of Mental Help Net from 1999 to 2011. Dr. Dombeck received his Ph.D. in Clinical Psychology in 1995 ...Read More

Interesting New ADHD Medication Under Study

The American Psychiatric Association recently had its annual convention, this time in Toronto, Ontario, Canada, and as per usual, a flurry of press releases describing various studies has been sent my way. One of them has caught my eye this morning, having to do with a new investigational drug intended for the treatment of ADHD called lisdexamfetamine dimesylate, or NRP104, for short. The hottest thing in drugs for ADHD these days seems to be the concept of buffering. Buffered drugs are basically drugs which have been specially prepared to have a time-release effect; to enter into the body, blood and brain slowly rather than all at once. You’re perhaps familiar with buffering because of all the advertising for buffered aspirin you’ve seen over the years.


Why buffer a drug? Well – the biggest reason for buffering is often that doctors want a constant amount of drug in a patient’s body all the time. They don’t want drug levels to rise and fall after each administration. By using a time-release form of a drug that disolves into the body very slowly, they can help insure that drug levels will stay more stable in the body than might otherwise be possible. There are other reasons for buffering as well. Aspirin is buffered, I believe, because it tends to irritate people’s stomachs. By buffering aspirin, the irritating effect that aspirin would otherwise have is lessened and the drug becomes easier to take.

Another good reason to buffer a drug is to prevent someone from getting high on that drug. For the most part, ADHD is treated with amphetamine salts; a cousin to the street drugs that used to be called “Speed”, and which today is known as “Crystal Meth”. Amphetamine compounds used to treat ADHD can be abused just like street drugs. However, when they are taken in proper doses by appropriate patients (and ADHD patients are typically considered appropriate for this treatment) there is a paradoxical effect – the drug helps these patients to sharpen their attention to detail and to become less hyperactive; to bound around the room less. Though such drugs are undoubtably helpful, the risk of abuse, by patients, or by others they might give the drugs to, remains high. Doctors can reduce the risk that people will take ADHD drugs to get high with them by buffering the amphetamine compounds within the drugs, so that they will be slow-release only. Slow-release drugs just don’t provide the same “punch” that unbuffered drugs will, and so they become less interesting to addicts and recreational users.

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The drug companies have been investigating a number of different ways to buffer their amphetamine compound drugs. Daytrana is a new ADHD preparation sold by Shire which uses a skin patch method of delivery to buffer the drug. The drug is contained in a fabric patch and absorbed through the skin to have its effect. Skin absorbtion of any drug is inefficient and will slow down the rate at which a drug becomes available. No self-respecting addict prefers “absorbable” drugs. They tend to prefer routes of administration which make a lot of drug available to the body in a hurry. IV needle injection into the blood is a good way to do this, as is smoking, or snorting of drugs.

NRP104 is interesting becuase it represents a new way to buffer an ampetamine compound. NRP104 is not an amphetamine itself – it is an ampetamine precursor. More accurately, it seems to consist of amphetamine compounds that have another small molecule glued onto them at the chemical, molecular level. The extra molecule (a naturally occuring protein called l-lysine) changes the shape of the ampetamine molecules and makes them inert and incapable of producing their normal “upper” effect. The human body is capable of acting upon the NRP104 molecules, however, so as to saw the l-lysine protein off the rest of the ampetamine part, effectively splitting the drug into separate amphetamine and l-lysine componants. I’m not at all sure what happens to the l-lysine, but the amphetamine (once released from the l-lysine) starts doing its normal speedy thing. So the beauty of NRP104 is (theoretically) that it is difficult to abuse, and difficult to overdose upon. The natural speed with which the body will break the NRP104 down into ampetamine will limit the amount of drug that is experienced by patients at any given moment. If they take more of the drug (in an effort to get high), the body will still just produce the same amount of amphetamine that it normally would in the presence of NRP104 – it can only go so fast. I have no real idea what would become of the undigested extra NRP104, but I presume that it would be excreted from the body still in an undigested form. Assuming that this sort of thing can be made safe for human consumption, and assuming it can be made to deliver the right dose of amphetamine to needy patients (two very big assumptions indeed), it does represent a very clever buffering technology; one that might make ADHD drugs into safer things all around.

More information on NRP104 can be found here.

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