Who decides what’s an analog of a controlled substance?
Dec31

Who decides what’s an analog of a controlled substance?

In this quiet week of reflection around the blogosphere, it makes sense that I should put up one last post on the topic that has brought us the most attention this year: synthetic cannabimimetics that have been sold in herbal incense blends such as K2 Spice. While marketed as “not for human consumption,” these products exemplify the growing legal highs industry (Coffeesh0p.com, a UK company run by John & Jo, pictured right, is a well-known example.). Let’s take a moment to re-hash (I can’t help myself) these marijuana mimics before getting to the question posed in the title. This series of compounds first synthesized by the laboratory of John W. Huffman at Clemson were originally investigated to establish structure-activity relationships for non-cannabinoid agonists at CB1 and CB2 endocannabinoid receptors. (See this post for more background from us and others about these compounds.) That is, Huffman and his collaborator, the late Billy Martin, were testing what structures similar to or different from the naturally-occurring compounds in marijuana could still allow high potency binding and modulation of these receptors. Endocannabinoid inverse agonists have been explored by several pharmaceutical companies as anti-obesity drugs via appetite reduction (the opposite effect of marijuana). Unfortunately, many of these compounds have failed – rimonabant (Acomplia), most notably – due to increased risk of depression and suicide. Carmen Drahl had an extensive 2009 C&EN cover story on these compounds and other anti-obesity strategies. But the Huffman compounds and others in herbal incense products are endocannabinoid agonists that produce sensory experiences similar to marijuana, albeit in a dose-dependent manner. As with any drug, too much can produce adverse reactions. All year, US municipalities and 15 states have criminalized the sale, possession, and/or use of products containing these compounds as hospitals and poison control centers began tallying cases of users seeking medical attention for extreme anxiety, hallucinations, and even seizures. Although a few deaths were at first associated with Spice products, other drugs were ultimately implicated in the one Indiana case that received the greatest publicity. This blog is not a formal reporting entity but we’ve accumulated a couple hundred comments across our posts in the various iterations of Terra Sigillata and the new Take As Directed blogs that existed during 2010. Those comments are about equally split as to the real health risks with these psychoactive compounds. Some readers were of the mind that inexperienced adolescent users were simply using too much of the products and experiencing panic attacks. Here, we’re talking about medically-classified panic attacks, described here at WebMD, where individuals feel intense terror together with autonomic symptoms that further reinforce the fear, even to evoking a sense...

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ScienceOnline 2011 Hotel Update
Dec27

ScienceOnline 2011 Hotel Update

As we excitedly approach the ScienceOnline2011 unconference in currently-snowy Research Triangle Park, North Carolina, we now have to open a second hotel for those who have not yet made their arrangements. Much of the extensive demand appears to come from word among the paparazzi that C&EN’s Rachel Pepling, Carmen Drahl, and Lisa M. Jarvis will be in attendance. The very kind folks at the Radisson RTP – Mr. Leon Bullard, I’m looking at you – are once again offering to us their US$72/night rate. While the Radisson is not the headquarters hotel (the Marriott will be the site of the Friday workshops), Mr. Bullard informs us that free Radisson shuttles will run between to the Sigma Xi Conference Center and the Marriott. To book rooms at the Radisson, use this special URL: http://www.radisson.com/scienceonline The room rate should be available from Wednesday 12 Jan through Tuesday 18 Jan but please let me know (by Gmail to abelpharmboy) if you are having difficulty getting the special rate. The hotels and conference sites are actually quite close together. In addition to the map Anton has at the conference website, I put together the one below with only the pertinent sites in the RTP area. View ScienceOnline 2011 Lodging in a larger map By way of distances, one can easily walk from the Radisson to Sigma Xi on an asphalt trail that runs just over a mile between the two facilities. The Marriott is a bit futher – another mile from the Radisson – but shuttles will be running across all three sites. Although we have just experienced a slightly unusual cold spell and snow for this area, mid-January temperatures in the area average a high of 53°F/12°C and a low of 30°F/-1°C.  We have had some years with temperatures near 70°F/21°C and others where it snowed during the conference. Half of the excitement of the conference and the weather is that you never know just what you’ll get. We’re delighted that you’ll be joining us in a few short weeks. Click here for current Durham, NC, weather conditions and forecast...

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The Man Who Gave Us Epo
Dec20

The Man Who Gave Us Epo

I learned over the weekend via this tweet from Serena Stockwell at Oncology Times that Eugene Goldwasser passed away on Friday at age 88. The biochemist and renal physiologist who spent most of his career at the Argonne National Cancer Hospital and Department of Biochemistry and Molecular Biology at the University of Chicago (web page) demonstrated that a hormone made in the kidney could increase the number of new red blood cells, a major advance in physiology. His laboratory purified the protein hormone, erythropoietin (or Epo), from sheep in 1971 and from humans in 1977. While a remarkable discovery of its own, Goldwasser’s partnership with then-Applied Molecular Genetics (Amgen today) led to the first- and second-generation recombinant biopharmaceuticals, erythropoietin and darbopoietin, and other versions such the the PEGylated EPO, Mircera. These drugs have transformed the lives of kidney dialysis and cancer patients, raised a furor in competitive sports – cycling in particular – and have been central to some of the most robust legal wrangling and medical costs discussions of our generation. Serena pointed me toward this obituary by Merrill Goozner, who devoted an entire chapter to Goldwasser in his 2004 book, The $800 Million Pill – sounds as though I have another book to go on my Christmas list. Goozner noted that Goldwasser, a Brooklyn native, attended the University of Chicago in the biological sciences and worked during World War II on scientific approaches against chemical warfare agents. I could find only one publication on Goldwasser’s work in this regard – not a surprise as much of the work is likely to have been classified. This 1947 paper appeared in the Journal of Pharmacology and Experimental Therapeutics (1947; 89:1-13) describing work in 1942 and 1943 on the use of 2,3-dimercaptopropanol (dimercaprol) against the vesicant (blistering) war agent, Lewisite – chlorovinyldichloroarsine or 2-choloroethenyldichloroarsine (an arsenic compound having nothing to do with this month’s arsenic adventures.). Goozner notes that Goldwasser completed his doctoral work at Chicago after the war and worked at the Argonne Cancer Research Hospital, a US Atomic Energy Commission-supported institution on the University of Chicago campus. This 1953 NEJM editorial notes that the hospital was headed originally by Leon O. Jacobson, a physician who together with Goodman and Gilman at Yale popularized the use of one of the first synthetic chemotherapy drugs, nitrogen mustard, a therapeutic derivative of chemical warfare agents that exhibited efficacy against leukemias and lymphomas. (As an aside, Goldwasser wrote a beautiful history (PDF) of his mentor and collaborator, “Jake,” for the National Academies Press after Jacobson’s death in 1992.). Goldwasser began investigating the regulation of the blood-forming elements and demonstrated in this 1956 Nature...

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The Future of Chemistry Jobs – Keep Reading and Commenting

Today marks the conclusion of a series of excellent blog discussions on the current state of the chemistry job market as led by Prof Matt Hartings at ScienceGeist (well, that’s who sent the press release), Chemjobber (opener and closer), Leigh Krietsch Boerner here at Just Another Electron Pusher, and Paul at ChemBark. Here’s the quick list with descriptions from Matt: • Monday, December 13: “We Are The Grist” at Chemjobber — an introduction to the topic and discussion of immediate ways to help clear the backlog of unemployed chemists • Tuesday, December 14: “Too Many PhDs?” at Just Another Electron Pusher — an in-depth look at whether there are too many chemists on the job market • Wednesday, December 15: “Time’s Up for Tenure” at Chembark — a critique of the current tenure system and how it influences academic competition • Thursday, December 16: “How Do We Break This Cycle” at ScienceGeist — an overview of governmental policies related to science and technology and their impact on employment in these fields • Friday, December 17: “The Future of Chemistry Jobs: Recap and Thanks” at Chemjobber — a summary of discussions initiated by each daily post. I’ve had a bit of a different slant on the topics because I’m a pharmacologist who works with chemists rather than a card-carrying chemist (well, I do carry a ACS card). Many of the issues are shared across the sciences and an argument still exists as to whether we in the US are doing better or worse with unemployment relative to the national average. The only place where I felt truly qualified to contribute was with my concern about ChemBark’s willingness to let tenure fall to the wayside. However, a discussion that emerged there and was addressed by Chemjobber was one threat that perhaps was not apparent to him in his R-1 institution: the proliferation of poorly-paid, no-benefit adjunct positions in chemistry departments at teaching-intensive institutions. Loss of tenure would open the door to institutions that would willingly dump you for lack of extramural research funding and replace you and your teaching load with unemployed chemist educators at a total of 1/4 to 1/3 your salary. As universities have taken an unvarnished business approach over the last two decades, I do not trust higher administration at all institutions to act in the best interest of faculty and the discipline of chemistry when financial pressures come to roost. British contributors to the discussion did not feel this was a problem there where tenure was eliminated in the late 1980s. As with any discussion about job prospects, particularly by academicians, is what constitutes a “chemistry job.”...

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Five years of Terra Sigillata
Dec15

Five years of Terra Sigillata

Today is my sister’s birthday – Happy Birthday, Sandi! (and keep an eye out for the FedEx truck today..wink, wink.) Five years ago, I chose to start this blog on my sister’s birthday so that I’d always remember my blogging anniversary (I’m not fond of the portmanteau, “blogiversary.”). Mind you, I also got married in 2000 thereby making it painlessly simple to know how many years I’ve been married, a task I should be able to accomplish well into senility. Five years ago, I was out of the academic environment and wanted a venue to both chronicle and share ideas I had about pharmaceuticals and alternative medicines. At the time, and still today, a great deal of information on the internet regarding herbal medicines is provided primarily by entities selling such products. With a background in natural products and degrees in pharmacology and toxicology, I felt that I could provide some truth and add perspective on those marketing claims and other sensationalized information on the web. I was also very fond of the short, pharmacology news notes that I used to give to launch my pharmacology lectures at the University of Colorado School of Pharmacy during the 1990s. These short updates on drugs in the news were and remain an important part of my approach to teaching by giving students a current context in which to apply classroom knowledge. Moreover, following developments in therapeutic areas outside of cancer (my main focus) got me to read primary literature outside of my field that was necessary to keep all of my other pharmacology lectures up-to-date. Among these vignettes I would also sprinkle a bit of history of pharmacology, biology, or chemistry. I had a great department chairman when I was in graduate school at the University of Florida – Allen Neims, MD, PhD – who would hold informal morning sessions with us to go over classic papers in pharmacology and challenged us to think whether we would have recognized the significance of the papers at the time. For example, we covered this 1938 paper by Merritt and Putnam in the Archives of Neurology & Psychiatry which represented one of the first structure-activity approaches to drug development, improving on the antiepileptic activity of phenobarbital with the comparatively less sedating drug, phenytoin (Dilantin), still used today. The exercise not only gave us an appreciation for our history but also helped us look at the current literature with a discerning eye. (Yes, Dr. Neims – I still remember this stuff.) In my original 15 December 2005 post, “A Humble PharmBoy Begins to Sow,” I cited my further inspiration by a David Secko article in The...

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