Chemistry and Life

Medicinal chemistry. Pharmacology. Toxicology. Environmental sciences.

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Methylhexanamine (also called 1,3-dimethylamylamine or DMAA) is a stimulant drug invented in the 1940s that was once used as nasal decongestant.  Even though it was withdrawn decades ago as a pharmaceutical drug, it is used as an ingredient in some marketed “energy boosting” supplements.

Normally, synthetic pharmaceutical drugs cannot be used in dietary supplements, but it has been claimed that methylhexanamine is natural and can be found in the oil extracted from geraniums.  In the United States the FDA generally does not have the authority to regulate natural chemical compounds this way.

There is at least one scientific report suggesting that geranium oil does indeed contain trace amounts of methylhexanamine.  A more recent and more thorough study that used multiple research labs and multiple plants types from multiple sources failed to find even a trace of methylhexanamine in any sample.  Nevertheless, for many years, the FDA did not intervene because it was potentially natural.

So if a supplement claims to contain methylhexanamine because it uses geranium oil, then the consumer is getting only uselessly small amounts of it, if any.  And if a “natural” supplement does contain a pharmacologically useful amount, then it is surely adulterated with synthetic material produced in a laboratory.

In recent years, potential hazards associated with consumption of methylhexanamine-containing supplements have concerned the FDA enough for them to take action.  Elevated blood pressure, cardiovascular problems, shortness of breath, tightening of the chest, heart attacks, and even death have been reported.    So the FDA does not currently permit supplements that contain methylhexanamine to be sold in the United States.

This just goes to show that the regulatory scheme in the US where natural ingredients with pharmacological effects cannot be regulated the same way that synthetic ingredients are is unjustifiable.  It is predicated on the falsehood that anything natural is inherently safer than anything synthetic.  And unless you study at the Gwyneth Paltrow School of Toxicology (“I don’t think anything that is natural can be bad for you”, she reportedly said), you know that some of the world’s most dangerous substances come from plants and animals.  How many people suffered health problems (or even died!) because of a tenuous claim that methylhexanamine is natural?

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An antiaging odd couple

A team of researchers, mostly from the Mayo Clinic and Scripps Research Institute, recently reported an interesting study.  They basically show that various cells that have stopped dividing (“senescent cells”) accumulate with age and that killing off those cells can extend the time that an animal remains healthy as it ages.

The researchers identified a combination of drugs that selectively killed these senescent cells.  When administered to mice, the drugs had the effect of “alleviating symptoms of frailty and extending healthspan”.  The drugs turned out to be an odd combination:  dasatinib, a drug used to treat cancer, and quercetin, a natural flavonol that is sold as a nutritional supplement.

As with much of journalism’s coverage of scientific work, the news reports are a bit exaggerated (or copied uncritically and essentially word-for-word from a glowing press release, such as in this Science Daily article).  The drugs used in the combination are probably far from being ideal drugs for this potential new use.  Dasatinib has the kinds of serious side effects that are tolerable when treating a potentially fatal disease, but wouldn’t be for someone who is essentially healthy.  Quercetin, like most flavonoids, is not that bioavailable with most of what is ingested getting quickly metabolized or excreted.

Whether this work will be “transformative”, as the authors claim, remains to be seen of course.  Extending the healthy life of a mouse is not necessarily going to translate to doing the same thing in a human.  Humans already have done a great deal to extend life expectancy and to maintain health into old age through various changes in society, lifestyle, and medicine.  To a certain extent, the system has already been optimized, so any further optimization will be increasingly more difficult.

But this is fascinating work that is certainly worth following up on.  No doubt these researchers already are, and probably others will join in looking to confirm and build upon these results.

The paper is published in the journal Aging Cell, which is open access, and can be obtained here:

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What drugs are being used experimentally to treat ebola?

With ebola in the news so much these days, I became curious which pharmaceutical drugs are being used to treat patients. I haven’t come across the information in any one place, just scattered among news articles and other sources. So I decided to put together a list myself. There aren’t any drugs approved specifically for treating ebola, but apparently several antiviral agents are being used experimentally. They are mostly drugs developed (or in development) primarily for treating other viruses.

    • Brincidofovir (CMX001) – An experimental antiviral agent which is a prodrug of the approved HIV medication cidofovir (Vistide). It belongs to the class of drugs known as nucleoside analog. The first person with ebola in the United States, Thomas Duncan, received this drug.
    • Favipiravir (T-705) – This is an antiviral agent that has activity against a variety of viruses. It is approved in Japan for use against influenza.
    • Lamivudine – HIV drug used in Liberia
    • ZMapp and ZMab – Related monoclonal antibodies. Both have been used in ebola patients in the United States and in Spain
    • BCX4430 – Experimental broad-spectrum antiviral and nucleoside analog. The National Institute of Allergy and Infectious Diseases (NIAID) is funding additional research and drug production.
    • TKM-Ebola – Has been used in one patient who was infected in Africa and brought to the United States. It is a combination of small interfering RNAs.
    • JK-05 – Several news articles describe this as “an experimental anti-Ebola drug developed by the Chinese military” that is “already approved for emergency military use” and has been sent to Africa, but I can’t find anything specific about what exactly it is or whether it is actually being used yet during the current outbreak
    • FGI-103, FGI-104, FGI-106 – I haven’t found any news references to these compounds currently being used experimentally during the current ebola outbreak, but there are animal studies reported in the corresponding Wikipedia articles

There are also vaccines such as VSV-EBOV under development.  These can’t be used to treat infected patients, but are instead intended to prevent the spread of the disease.

If I have missed any other drugs that have been mentioned in the news but aren’t on this list, please let me know and I’ll add them.



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Cranberry juice and peanut allergies

As the parent of a child with a peanut allergy, I found this article in Chemical & Engineering News intriguing. Researchers are exploring the idea of treating such allergies by combining peanut flour with polyphenol-rich foods. Polyphenols are a class of chemical compounds found in some foods, particularly dark-colored fruits. In this research, extracts from cranberries, grapes, black currants, chokeberries, and elderberries were used. Polyphenols are believed to limit some types of immune responses. When the peanut flour and fruit extract combinations were fed to mice which had been sensitized to peanuts, the researchers indeed found signs of a reduced immune reaction.

This doesn’t mean you should try feeding peanuts and cranberry juice to your allergic children. But this at least shows some potential to improve the immunotherapy procedure where patients are given small doses of an allergen under controlled conditions in order to help them gradually build up a tolerance.


Crocuses, crocetin, and transcrocetinate sodium

Crocuses Michael H ParkerA few days ago we got an early Spring dusting of snow.  It melted shortly after the sun came up, but the snow and budding crocuses together made a nice photo before it was gone.  Taking this photo brought to mind a nice story connecting crocuses to a potential pharmaceutical drug.

Crocuses are the source of the spice saffron which gives a bright yellow color to the foods it is used in.  The part of the plant that is used is the little yellow stigma inside the flower.  The chemical that is primarily responsible for that yellow color is called crocin.  Crocin is a glycoside (a sugar derivative) of crocetin which belongs to a class of pigment compounds called carotenoids.  When crocin is reacted with sodium hydroxide, crocetin is released as the sodium salt.  It is this salt of crocetin that is being studied as a potential pharmaceutical drug.

The generic name assigned to this compound is transcrocetinate sodium.   And according to this document, it is being studied as a “radiation sensitizer for tumors” and for “reoxygenation of hypoxic tissue in peripheral artery disease”.  The company behind the research is Diffusion Pharmaceuticals which is studying related carotenoids as well.

I don’t know how promising these compounds are in terms of their development and clinical trial results, but it would certainly make a nice ending to the story if a chemical compound from crocuses ending up as a useful medicine.



Tenapanor, the “salt-buster”

Tenapanor (AZD1722, RDX5791) is a drug currently under development by Ardelyx and Astra-Zeneca.  It is designed to prevent the absorption of sodium from the salt in food.

It is an inhibitor of a protein called non-absorbed solute carrier family 9 sodium hydrogen exchanger member 3.  (That’s quite a mouthful, so it is referred to as an NHE3 inhibitor).  Your body needs a certain about of sodium to function properly, so it has a mechanism for extracting it from food in your digestive system.  Basically, tenapanor blocks the action of this mechanism, preventing it from transporting sodium across the gut lining into the blood.

Chemical structure of tenapanor

Chemical structure of tenapanor

Tenapanor is putatively aimed at patients with kidney disease and other health problems that make them very susceptible to adverse effects of high salt intake.  But no doubt, there are also visions of a lifestyle drug that can be taken by anyone.  Just like the way that weightloss drugs which are approved for use in severely obese patients are sought after by people looking for a quick way to loose a few pounds.  The temptation to find a drug to solve the problem rather than to change one’s bad habits is just too great for some.

Tenapanor is already being referred to in the media as a “salt-buster drug” (here, for example) giving it the same type of appeal as the latest “fat buster” being advertised.  The idea is that maybe someday you can eat all the potato chips you like without worrying about the salt affecting your high blood pressure.

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Health benefits of dark chocolate

There have been a couple of scientific studies on the potential health benefits of dark chocolate reported recently:

Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men (Mar 2014), The FASEB Journal, 28(3), 1464-1473

The effect of acute dark chocolate consumption on carbohydrate metabolism and performance during rest and exercise (2014), Applied Physiology, Nutrition, and Metabolism, 39(2): 173-182

Dark chocolate and vascular function in patients with peripheral artery disease: A randomized, controlled cross-over trial (Feb 2014), Clinical Hemorheology and Microcirculation

Dark Chocolate ‘Treats’ Vasculature, but Added Flavanols Don’t Help, MedScape

These studies are, in general, small scale and the results are somewhat ambiguous.  But I don’t need to wait for the science to catch up and I’m starting a supplementation routine now.