The Half Decent Pharmaceutical Chemistry Blog

Last Sunday I went to Venice to complete this year’s visit to the Biennale, before its closing day (which is tomorrow). The weather was…predictable and not bad: a cloudy and chilly day in Venice is, in my opinion, the best you can get in this period. What’s more, I really enjoyed the trip from the railway station to the exhibition site on a so-called water bus: the see was not too rough but I nevertheless liked staying on the deck very much. That’s because I like the see very much and so far, I’ve never been sick on a boat, whatever the conditions.
The Biennale itself, this year, was pretty good too. On this very occasion, I visited the Old Arsenal building only, where you generally have less stuff and therefore, much more time to see every installation. I also met two guys form Basel, Switzerland: one had Italian origins and told me he was a member of a hip-hop group called Tre Cani (Three Dogs). Briefly, he was there not only as an art student, but also to shoot a scene for his band’s next video clip. I’ll admit that Switzerland and hip-hop music seems a weird combination, but the guy looked very motivated and wasn’t the gansta kind of rapper. Mind you, check out their website on myspace.

Anyhow, as I’m sure you know, most of the exhibitions of the Biennale are located at the Giardini, which I visited, back in September. There, you have the national pavilions, surrounded by a peaceful garden: so, you can go there only in the summer.

I was pretty impressed by a 1991, untitled (as usual) installation at the American pavilion. The floor of a room was pretty much entirely covered by liquorice rods, each of them neatly wrapped in cellophane. The light in the room created an strange and evocative atmosphere. And I have to say I quite proud of the picture I took there.
Still, when it comes to picture of liquorice, nothing can’t beat this one, which seems to be taken straight from a 1300s book, where some monk kept record of his poisons and drugs.
Poisonous as liquorice can be. Yes: you look at a rod of liquorice and think that it doesn’t look that dangerous. I mean, it often kill your hunger, if eaten before supper. That’s something your mother or granny has always told you, hasn’t she?
Besides, the roots of Glycyrrhiza Glabra are very good-looking and no wonder an artist thought of this legume for one of its works of art: dark on the outside, with a bright yellow fibre inside.
Its active principle is an awesome triterpenoid glycosidic saponin called glycyrrhizin, with plenty of useful activities. Once the glycosidic bond is hydrolysed, glycyrrhetic acid is freed and this substance is an emollient, an expectorant, an aromatiser, a mild laxative and even milder spasmolytic More recently, it’s reported to be increasingly tested as an indirect-acting anti-ulcer medication. Glycyrrhetic acid inhibits the local, catabolic metabolism of prostaglandins, which act on primary gastric cells, through binding to their receptors, enhancing the secretion of protective mucous and reducing that of hydrochloric acid.
This new function has lead to a synthetic analogue of glycyrrhetic acid called carbenoxolone, launched on the British market as a treatment for oesophageal ulceration and inflammation.

That’s all very appealing and reassuring, but not that fast on that. Glycyrrhizin not only impairs the catabolism of prostaglandins, but it also affect aldosterone. An excessive use of liquorice, therefore, can cause edema, hypokalemia, sodium retention and hypertension. That’s why there’s even a toxic dose for people suffering from hypertension and it’s actually rather low: 150 mg. This explains all those glycyrrhizin-free liquorice preparations available.

My favourite Looney Tunes character has always been Taz, the Tasmanian devil. However, my opinion on him has radically changed since I read of a distinctive feature of Tasmania: this region is a massive producer of opium straw. So, in case you’ve ever wondered what kind of force powers Taz’s whirring around, now you have the answer: heroin-craving.

Junkies’ favourite holiday destination, in the Seventies, wasn’t Tasmania, though. Before it became the nightmare it’s today, Afghanistan was a popular site for heroin addicts, where they could easily find cheap heroin, as this country almost entirely relied economically on poppy cultivation (an old tradition that, despite all the recent political events, seems to continue), and breath-taking landscape to garnish their trips. Although Australia and Afghanistan are, well, as different as chalk and cheese, their climate is not that different: poppies need a lot of sun to grow vigorously.

The green capsules of Papaver Somniferum are incised from April to June, when it’s still immature, at midday: from the cut, a white juice begins to come out but, given that it’s midday, so it’s likely to be very hot, it dries rapidly. The next day the dry product is collected in cakes which are often placed in the sun for an additional cycle of drying. The same capsules can be incised every 3 or 4 days throughout the harvest time.
Heroin, of course, isn’t found directly in the plant extract: morphine, the major component of the white juice has to be acetylated to yield heroin.

But, of course, morphine isn’t the only substance to be collected from poppies: it actually contains 25 alkaloids (either phenantrene or benzylisoquinoline derivatives). The most abundant, after morphine, are codeine, noscapine, narceine and papaverine.
From a pharmacological point of view, codeine is, of course, the most interesting one, due to its well-known antitussive properties.

Having just finished working at a chemist’s, I think it’s important to remind that, in the past, opium used to be the main ingredient in a galenic preparation called laudanum. This is basically an alcoholic solution (normal red wine was often chosen), where cloves, saffron and cinnamon leaves are employed to improve the bitter taste of opium. Although the high levels of morphine undoubtedly guarantee analgesic effect, the presence of all the other poppy alkaloids (some of which toxic) explains why this remedy is no longer administered. More importantly, though, laudanum has always been a drug of abuse, in part because of the alcohol content. 

Today is national holiday in Italy. On this day, people celebrate what happened on April 25, 1945: the end of the Fascist regime and of the Second World War. In descending order.

Believe it or not, I've found a link between Fascism and pharmacognosy: Ricinus Communis.

If you're Italian, you'll be actually thinking this is very predictable and banal; but if you aren't, then, there is a chance you totally ignore what an important role castor oil played before and during Fascism.

Ricinus Communis is a plant which grows remarkably well  in Italy (and in the Mediterranean area), where it can easily reach a height of 2 meters. It's rather good-looking, with its big, green and reddish leaves and the two types of flowers (male and female together, on the same plant).


 
The seeds are protected by a tough, thick, oval, marble-grey and brown coat. They contain the components of the (in)famous yellowish oil, with its disgusting taste.

Although they are the source of a drug which, as I'll explain later, it's still used in many parts of the world, two seeds are lethal if ingested: that's because they also contain a toxin called ricin, dreadfully prone to cause hemagglutination, which is denatured when the oil is extracted.



The major ingredient of castor oil is ricinoleic acid, which is probably the best-known of the stimulant laxatives.



Generally speaking, the mechanism by which these drugs work remains partly unknown, but for what concerns ricinoleic acid, it's not that complicated to link its irritating action on the intestinal mucosa to the catastrophic consequences: the intestine becomes unable to absorb anything, including water.

There are concerns over long-term consequences of a prolonged use this kind of laxatives: dehydration, electrolyte imbalance and chronic loss of intestinal ability to absorb food and liquids, which may eventually lead to malnutrition.

Moreover, ricinoleic acid can't be administered during pregnancy, because of the strength of intestinal contractions.

Last but not least, some think these drugs induce dependency and cause destruction of the myenteric plexus.

The main difference between castor oil and the other stimulant laxatives is latency: the effect of ricinus communis is dramatically quick.

This drug, though, is still prescribed: in poor countries it might be chosen due to its incredibly low price, but also in industrialized countries the use of castor oil hasn't disappeared, yet.

The oil was also the favourite choice of Fascists during interrogatories: it's easier to obtain information from someone who has just had a glass of prime quality castor oil, isn't it?

There is a superb, old film, from an Italian director (Federico Fellini), called Amarcord: the action takes place in the 1930s, in Italy (not too far from where I live).



If I were you, I'd watch it (in your mother language or, even better, with subtitles): not only does it provide a vivid, oniric fresco of that period, but it also shows how castor oil also served as a punishment for minor crimes (especially for people who dare to criticize the regime).

Last night I watched "A Clockwork Orange" and, perhaps because it was the first time as student of industrial pharmacy, the scene at the Korova milkbar made me particularly think.

Why milk-plus? Why not tea-plus? Because tea would make much more sense.

Let me explain: this is a lovely picture of Myristica Fragrans, or nutmeg, a tree indigenous to Indonesian islands.



The most interesting part of this evergreen plant is the brown nut, which is pretty tough and has a rough tegument.

Nutmeg contains different substances, but mostly myristicin, which is well-known for its eupeptic properties: the dried kernel of the seeds is grated on food, where, not only does it add a spicy flavour, but it also eases digestion.

Nevertheless, if you actually look at the chemical structure of myristicin, you'll realise it's not that different from a catecholamine.

What's more: myristicin has central activity too. In this case, the effects dramatically remind of those produced by mescaline.

Mescaline is a potent hallucinogen extracted from the peyote cactus. In particular, at the top of the plant there's a button, which is remarkably rich in this sympathomimetic.

Briefly, what mescaline does is to increase blood pressure and body temperature, probably inducing a massive release of norepinephrine; moreover, it causes anxiety, terribly realistic hallucinations, odd as it may sound, and illusions. This means the drug can deform the perception of reality.

This "magic-button" was largely used by the priests of central American religions to establish a deeper connection with divinities.



Let's go back to nutmeg. Junkies undoubtedly like it when they can't afford to buy heroin any more. In fact, whereas two nuts kill a normal person, SIX result in hallucinations in an addict.

Certainly, such a huge amount of nutmeg can't be sniffed: spicy as it is, this would have rather comic results.
Besides, myristicin reaches its highest effectiveness when orally administered. Once again, how could you swallow so much powder without, say, vomiting?

So, ingenious junkies have deviced a way to introduce myristic by oral route: they usually grate nutmeg in tea and, then, drink what, in my opinion, is one of the most disgusting cocktails one could possibly prepare.



Still, when you reach a certain level of addiction, I imagine this is a price you are ready to pay to feel slightly better.

Maybe milk could be used for this very purpose, so, "vellocet or synthemesc or drencrom" could be replaced by myristicin.

Yes, we had to wait but, finally, Spring is here!

Of course, for this worrying delay we must blame global warming, that has caused one of the warmest winters ever, followed by a very cold, rainy and windy March and, perhaps, hot and humid spring.

By the way, it's time to go out and appreciate the awakening of nature. Spring, however, is also a frightening period for people who suffer from allergy.

So, there you are: deadly and beautiful. Pretty much like Atropa Belladonna (or, Deadly Hightshade)



I must admit, the only reason I have begun to talk about pharmacognosy is because I absolutely adore pictures like the one above: these old(ish) images are really evocative and relaxing, in my opinion.

Atropine has been the protagonist of an episode of Saturday Night Synthesis and is something students of (industrial) pharmacy deals with rather often.

Almost a month ago, for example, I said I took home a large quantity of atropine powder from a lab-course I did last year. In that period, in fact, we were learning how to prepare some of those drugs pharmacists produce in the lab in the back.



Atropine is the major alkaloid extracted from the roots and leaves of the plant. Scopolamine is the second component in terms of quantities.

In the ancient times, this plant was extremely popular among desperate housewives: somehow, it reminds me of botox. Like that toxin, everyone perfectly knew Deadly Nightshade was a poison, but they used it to have beautiful, sexy (?) eyes, with enormous pupils, anyway.

Women were aware of its toxicology as well: small quantities, given on a daily basis, little by little kill without apparent cause (before CSI, of course).

So, theoretically, a lady could slowly murder her husband while looking for a younger and hotter one.

Really efficient, indeed, but, even as a mydriatic it's very poisonous.

The plant is also incredibly good-looking. The leaves are quite big, long and acute at the apex.



The flowers are purple and have the shape of a bell. A small, dark berry matures in September and it's smooth, juicy and sweet, but you'd better not try to eat it since it's incredibly poisonous.

A superb plant to grow in your garden. Pretty useful if you have troubles with your neighbours or just want a new partner...