Acetyl Fentanyl: Dangerous, Poorly-Named Street Drug
Aug30

Acetyl Fentanyl: Dangerous, Poorly-Named Street Drug

The U.S. Centers for Disease Control and Prevention has released a summary on a cluster of 14 deaths in Rhode Island earlier this year attributed to “acetyl fentanyl,” an analog of the potent, short-lived opioid used in pain management and outpatient anesthesia. The report, “Notes from the Field: Acetyl Fentanyl Overdose Fatalities — Rhode Island, March–May 2013,” appears in the August 30, 2013 issue of Morbidity and Mortality Weekly Report (MMWR). The first 10 deaths were reported in the Providence Journal on May 13, 2013, leading CDC officials to join the team in the investigation. A total of 14 deaths were identified. Samples from the decedents gave positive ELISA results for fentanyl but GC/MS revealed an analog that authorities are calling acetyl fentanyl. A CDC health advisory released in June briefly details the chromatographic pattern and mass spectra. Cayman Chemical Company, who offers the reference material, also calls it acetyl fentanyl, but offers desmethyl fentanyl as an alternative. The IUPAC name is N-​phenyl-​N-​[1-​(2-​phenylethyl)-​4-​piperidinyl]-​acetamide; fentanyl has a propionamide instead of the acetamide. A CBC news story described a late April series of drug busts in Montreal that included seizure of a compound they called desmethyl fentanyl. The current MMWR release also links to an alert from the Pennsylvania Department of Drug and Alcohol Problems that reports 50 acetyl fentanyl deaths in the state this year, through June 27th (PDF). Most curious is that the compound has not been described before as a recreational drug. It’s not available as a prescription drug anywhere in the world and is only a minor side product (0.04%) found in prescription fentanyl (DOI: 10.1016/j.jpba.2010.04.004). In a lengthy discussion on Twitter last night and this morning with Chemjobber, SeeArrOh, and others, I initially asked whether acetic anhydride could have been used to acetylate fentanyl, thinking — without looking at the structure — that it was truly acetylated. I found later that fentanyl is made from 4-anilino-N-phenethylpiperidine (ANPP) using either propionyl chloride or propionic anhydride. Hence, acetyl fentanyl could be made by reacting ANPP with either acetyl chloride or acetic anhydride (That’s the extent of my synthetic expertise, Dear Reader.). The major problem with acetyl fentanyl — or fentanyl for that matter — is its high potency relative to natural opioids like morphine or the more potent synthetic, heroin. As a result, the CDC recommends that emergency rooms and other facilities providing substance misuse care services stock up on the opiate receptor antagonist naloxone in anticipation of an increase in overdoses across North America. But it looks like we’re stuck with acetyl fentanyl as the name. Any...

Read More
The Cinnamon Challenge: On Being Charged with #Chemophobia
Apr23

The Cinnamon Challenge: On Being Charged with #Chemophobia

As many of you are likely to have heard yesterday, a paper from Steven Lipshultz, MD, at the University of Miami appeared in the journal Pediatrics detailing poison control center reports on an adolescent misadventure called The Cinnamon Challenge. The challenge: to swallow a teaspoon of cinnamon powder in 60 seconds without any liquids. The practice has been rummaging about the internet since 2001 but really took off on YouTube over the last three years. Lipshultz’s report discusses the risks of such tomfoolery, particularly due to the inhalation of cinnamon powder while one is choking. I planned to write about this practice both here and at my Forbes.com blog since I thought both chemists and the general public would be interested in the topic. I wrote the Forbes post earlier this morning and drew a series of comments from a kindly San Diego-area chemist who took issue with my facetious comparison of cinnamaldehyde (cinnamic aldehyde) to formaldehyde. While Lipshultz states that much of the acute pulmonary toxicity of cinnamon powder is likely due to the cellulose content, I submit that some damage could be due to protein adducts formed by cinnamaldehyde. Yes, yes, it’s not as dangerous as formaldehyde. But even at roughly 1% (w/w) in the powder, I hypothesize that the cinnamaldehyde could cause epithelial damage. Also note that cinnamaldehyde is not just any aldehyde but rather an unsaturated aldehyde. That makes me think of acrolein. The experiments have not been done. But one animal study has been published showing that intratracheal administration of cinnamon powder — not pure cinnamaldehyde — can cause acute lung injury in rats and trigger pulmonary fibrosis within a month. Alas, my concerns about cinnamaldehyde rubbed two commenters the wrong way and one, well, sought to chemsplain me. I was originally trained in toxicology so I know the whole Paracelsan story that the dose makes the poison (to which I’d also add “route of administration”). But do you chemists, especially those in chemical toxicology, think that I’m overreacting (as it were) to the potentially reactive nature of cinnamaldehyde in inhaled cinnamon powder? I’m willing to be corrected if I appear to suffer from #chemophobia. But I hypothesize that 1% (w/w) cinnamaldehyde can be...

Read More
Criminal Poisoning Arrest at a Hometown Chemical Company
Nov29

Criminal Poisoning Arrest at a Hometown Chemical Company

Here’s a brief on a sad story I came across while trolling for news at home via northjersey.com.  A former employee at a Carlstadt chemical plant allegedly attempted to poison a coworker’s coffee with an antifreeze ingredient and sprayed acid on her coat, Carlstadt Police said. [. . .] A supervisor had allegedly observed a video of DeJesus putting methanol, commonly used in antifreeze, into a coworker’s coffee, Carlstadt Det. John Cleary said. The chemist was also accused of spraying [t]richloroacetic acid, which is used to chemically peel skin, on the same employee’s coat, purse and workspace. These substances were part of the company’s inventory, authorities said. I think I understand why she’s a former employee. The accused listed her address in my hometown of 11,000, Wallington, just on the other side of the tracks (literally) from her employer, Sonar Products. The writer, Meghan Grant of the South Bergenite newspaper, seemed to underestimate the risk of drinking methanol. She cited liver and kidney injury without noting that formic acid and formaldehyde metabolites could cause blindness in the victim. I left a note for Grant to keep us apprised on the status of the victim. Source: Grant, Meghan. Carlstadt chemist accused of poisoning coworker. South Bergenite, 15 November 2012....

Read More
Naming Genes Unlike Named Reactions
Oct29

Naming Genes Unlike Named Reactions

Our best wishes to all of you in the Northeast getting ready for Hurricane Sandy. I understand that even DC is closed today. So if you still have power at home, let me share a bit of levity with you. Over the weekend I learned that my science writing student, Meghan Radford (@meradfor), had a clever piece published at mental_floss, the magazine and website, “where knowledge junkies get their fix.” Megan’s article entitled, “18 Gene Names that Cover the Gamut, From Movies to Pop Culture to Cartoons,” illustrates the comical yet discordant and unscientific process behind naming genes. Her article reminded me of C&EN’s Carmen Drahl when she wrote about named reactions in both the magazine (C&EN, 17 May 2010) and her Newscripts blog here at CENtral Science. I’m not familiar with any genes that are named after the person who discovered them but, as Radford points out, a great many have been given interesting colloquial names. International gene nomenclature organizations exist but the standardized rules of these committees still make refer to the less formal names. For example, the human “sonic hedgehog” gene is SHH. The name of the original Drosophila hedgehog gene, hh, made functional sense as described by Nobel laureate, Dr. Christiane Nüsslein-Volhard: fruit fly embryos with mutated hh expressed pointy extrusions called denticles and resembled hedgehogs. The mammalian homologue, Sonic was named after the Sega video game character. My favorite from Radford’s list is one I hadn’t known: INDY, for “I’m not dead yet.” Beyond this laboratory levity is a very serious issue for clinicians. From a 2006 New York Times article by John Schwartz: A gene with a funny name may be linked to a medical condition that can be heartbreaking. The human variant of the fruit fly’s “hedgehog” gene, known as “sonic hedgehog” after the video-game character, has been linked to a condition known as Holoprosencephaly, which can result in severe brain, skull and facial defects. “It’s a cute name when you have stupid flies and you call it a ‘turnip,’ ” Dr. Doe said. “When it’s linked to development in humans, it’s not so cute any more.” But today, I take time to be proud of my student for pitching a story to mental_floss and getting published. You can also read more formal writing by Meghan Radford at her blog, Neural Expression. Source: Radford, Meghan. 18 Gene Names that Cover the Gamut, From Movies to Pop Culture to Cartoons. http://www.mentalfloss.com/blogs/archives/148072, 27 October 2012....

Read More
Smiles: 2C-I or not 2C-I?
Oct01

Smiles: 2C-I or not 2C-I?

Designer drugs in the news This is tiring enough for a science writer. I cannot imagine being in law enforcement. The pace at which psychoactive designer drugs are appearing on the street is about as challenging for me as keeping up with dietary supplement companies that adulterate their products with actual prescription drugs (an area I’ve been covering since 2007 but a practice that goes back decades.) This week’s designer drug hullabaloo comes to us courtesy of last week’s frightful murder-suicide by Sons of Anarchy actor, the late Johnny Lewis. ABC News is reporting today that Lewis was reportedly taking “Smiles,” a street name for 2C-I, the phenethylamine hallucinogen first synthesized by Alexander Shulgin. 2C-I is more properly known as 2,5-dimethoxy-4-iodophenethylamine. This structural analog of mescaline (3,4,5-trimethoxyphenylethylamine) was among a litany of designer drugs that was criminalized in the US back in July with the Synthetic Drug Abuse Prevention Act of 2012 (Cheryl Hogue had a nice discussion of the Act, including some quotes from yours truly, in the 27 August 2012 issue of C&EN.). But the psychedelic drug information website, Erowid, is proposing that the effects reported for “Smiles” are more likely due to the compound 25I-NBOMe (or 2C-I-NBOMe): the more complex and much more potent 5-HT2A agonist, 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine. The radiolabelled version of this drug was made, it turns out, by some radiochemistry colleagues down the road at RTI International and characterized by Purdue pharmacologist, David E. Nichols (Bioorg Med Chem 2008;16:6116-6123 DOI:10.1016/j.bmc.2008.04.050. Depending on your institutional access, the DOI may not work so you can view the PDF here through the NIH Public Access Program. Again, here is a case of where a laboratory tool has been co-opted by the recreational drug market, a case that Nichols himself lamented in Nature at the beginning of 2011. Why should the non-chemist or general reader care about this structural gobbledygook? 25I-NBOMe/2C-I-NBOMe is about 20 times more potent than 2C-I in binding those 5-HT2A receptors in the brain, the same ones that mediate the psychedelic effects of old-fashioned hallucinogens such as LSD and mescaline. This means that it takes a very low dose of this chemical — low, sub-milligram doses — to experience rather complex sensory and behavioral effects. Here at Erowid is a user experience after a very high dose reported at 3.75 mg – the individual had previously reported a “very enjoyable night” after taking only 0.75 mg. With an unemotional view of the user’s experience, I find it stunning that the human brain is capable of such complex sensory activity after being tickled with some synthetic molecules. But in the context of the Lewis murder-suicide, one would not...

Read More
Poisons and Policy: Arsenic and Aflatoxins
Sep20

Poisons and Policy: Arsenic and Aflatoxins

In the past 24 hours, do you recall hearing anything about arsenic in rice? If you’re in the United States, the answer is very likely, “yes!” A great many pixels were spilled yesterday when Consumer Reports and the US Food and Drug Administration released — almost simultaneously — analytical data on inorganic arsenic concentrations in 200 samples of commercial rice products, particularly those grown in the southern US. You can’t do any better in understanding this story than reading, “Arsenic and Rice. Yes, again,” on Deborah Blum’s Elemental blog at Wired Science Blogs. Professor Blum has been discussing arsenic in the diet for a few years, an interest she developed while composing her superb book, The Poisoner’s Handbook: Murder and the Birth of Forensic Science in Jazz Age New York. Deborah’s post puts in perspective the risks of inorganic (and organic) arsenic concentrations in food products such as rice relative to drinking water. Arsenic occurs in nature but exists in higher concentrations in water from areas where arsenical pesticides have been used in cotton farming or poultry deworming (the latter discussed in 2006 at NYTimes). While she closes in being critical of the FDA for lack of clear consumer guidance, let it suffice to say that no character in Blum’s book was killed by poisoning with rice from Louisiana. Pick your poison What caught my attention yesterday was a completely different report from the US FDA — actually a FDA ruling released by the Iowa Department of Agriculture and Land Stewardship. Corn containing one of the most potent natural toxins and carcinogens — a class of compounds called aflatoxins — can be legally blended with other corn for use in animal feed.  A standing rule of the FDA, when invoked, allows farmers to blend corn containing up to 20 parts per billion of aflatoxins with corn containing lower concentrations (or none) of the toxin family. Here’s where 20 parts per billion falls in the FDA’s guidelines according to the Iowa Dept of Agriculture statement: The FDA has established guidelines for acceptable aflatoxin levels in corn based on its intended use.  Corn containing aflatoxin in concentrations of greater than 20 ppb cannot be used for human consumption and cannot be used for feed for dairy animals or for immature livestock of others species. Corn containing aflatoxin at 100 ppb or less can be used in breeding cattle and swine and mature poultry.  Corn with 200 ppb or less can be used with finishing swine greater than 100 lbs. in weight and corn with 300 ppb or less can be used in finishing beef cattle. Where is this aflatoxin coming from...

Read More