The Pharmaceutical Journal Vol 267 No 7168 p488
6 October 2001

This article
Reprint
Photocopy

Method, not substance
Death in the Alps
Naming the name

Method, not substance

In the middle of the 16th century the Council of Lima made efforts to restrict the recreational use of coca leaves by the peoples of Bolivia, Chile and Peru, something which was traditional in the Andean region at the time. The Council stigmatised coca as “a useless object liable to promote the practices and superstitions of the Indians”. Nevertheless, the Conquistadors were glad enough to pay their mineworkers with coca leaves in order to extract more labour out of them. According to native South American legend, the Children of the Sun had presented the coca plant to the people of the early Inca empire “to satisfy the hungry, provide the weary and fainting with new vigour, and cause the unhappy to forget their miseries.”

While the population were confined to chewing quids of coca and lime, there were few instances of serious addiction problems associated with violence. Once cocaine was isolated, and people took to inhaling the vaporised base and injecting solutions of the salts, however, matters took a sinister twist. The important factor for those who wished to abuse the drug and ride high on its stimulant effects became the speed with which the alkaloid could be introduced into the brain’s dopamine receptor system. It is the same with many habit-forming drugs, and one of the great problems with some of them is the difficulty of presenting them in a form that does not encourage abuse for the sake of synthetic pleasure.

A paper published in JAMA for 22/29 August discusses the paradox of methylphenidate, a compound that has activity closely resembling that of cocaine, but which is used in the daily treatment of four to six million children in the United States suffering from attention-deficit hyperactivity (ADH) disorder. A psychiatrist from the Brookhaven National Laboratory has commented that methylphenidate taken in the regular tablet formulation by mouth rarely produces a “high” and appears not to be addictive. However, abusers claim that, if converted into a liquid form and injected, it gives a jolt resembling that experienced from cocaine.

Like its distant relative, methylphenidate decreases activity and increases ability to concentrate in persons affected by the ADH syndrome. By contrast half those without the syndrome describe its effect as unpleasant, resembling the effect of too much coffee.

The effects of methylphenidate have been studied by positron emission tomography, to examine how the dopamine system, responsible for reward and motivation circuits during pleasurable experiences, responds to the drug. Dopamine receptors activate a sense of unpleasantness when the signal is too strong, and one of boredom when it is insufficient. Dopamine molecules are recycled to their producer neurons by autoreceptors, half of which are blocked by cocaine.

In tests in 11 healthy men taking various doses of methylphenidate orally, more potent inhibition occurred than with cocaine. With a typical dose of 0.5mg/kg, such as is given to children, 70 per cent of dopamine transporters were blocked. High levels of extracellular dopamine, as seen after cocaine, were observed. But with children with attention-deficit hyperactivity disorder, dopamine transporters are more active than in healthy individuals, and this effect counteracts the liability to develop dependence, as happens by contrast with cocaine. Methylphenidate takes about an hour after an oral dose to raise neuronal dopamine levels, whereas inhaled or injected cocaine takes only a few seconds.

It is important to carry out further studies of the impact of methylphenidate on brain dopamine activity, since there are equivocal indications that suggest that children with the ADH syndrome may be more prone to developing addiction to other psychoactive agents than are healthy ones.

Back to Top

Death in the Alps

There is an interesting note in Science for 3 August regarding fresh discoveries regarding the celebrated Ice Man, Ötzi, whose mummy, believed to be 5,300 years old, was discovered not long ago in a glacier high up in the Tyrolean Alps and has been subjected to much examination since. It was argued at the time of the discovery that Ötzi had died alone while he was hunting game. The body was carefully preserved under refrigeration in the archaeological museum in Bolzano.

Under the supervision of Horst Seidler of the University of Vienna, the mummy was recently subjected to radiological examination, which revealed that an object was embedded in the shoulder. Computed tomography scanning then established that the object in question was a flint arrowhead some 2cm long which had traversed the ice man’s scapula and become buried 6cm deep under his shoulder. This missile had struck no vital organ, but by the evidence of dense tissue surrounding the wound it had produced extensive heavy bleeding. According to the pathologist of the Bolzano hospital, the poor victim probably suffered a prolonged and painful death, especially since considerable damage to nerves may have resulted in paralysis of his left arm.

The evidence points to the conclusion that Ötzi was shot by a bowman who was standing behind him and at a slightly lower altitude. The opinion of those who, in 1994, put forward the argument that he was a lone hunter who had collapsed from the effect of extreme cold or illness has therefore been discounted in the light of further research.

Back to Top

Naming the name

I am fast coming to the conclusion that the current spate of producing complex and linguistically barbaric non-proprietary names for new drugs is becoming intolerable. In the most recent pharmacovigilance report from the Medicines Control Agency I make the unwelcome acquaintance of rosiglitazone, pioglitazone and trastuzumab. Add these vandalisations of the language to grepafloxacin and apraclonidine and you end up with a fine array which would have delighted the Goth and Vandals. And this list is far from exhaustive.

Given access to a computer, which is by no stretch of the imagination an aid to civilised vocabulary, there is practically no limit to the string of crude Brobdingnagian invective that a keen language czar can produce at the touch of a button. In Jonathan Swift’s country of the giants, compared with the pigmy Gulliver, were produced things and people that were “Brobdingnagian”, meaning outrageously huge. When I come across some of the new names describing recently produced drugs, I feel deep sympathy with poor Gulliver.

Of course, it has to be recognised that the explosion of grotesque nomenclature has been going on for a long time, building up to a climax. A glance at the USAN (United States Approved Names) dictionary reveals a stunning selection, amounting to some 3,000 adopted names in addition to coded designations and registry numbers.

The dictionary sets out the guiding principles for coining names. One particularly interesting rule states: “Attributes that contribute to usefulness are simplicity, with respect to both brevity and ease of pronunciation, and those qualities that lend euphony and enhance ready recognition and recall”. A let-out clause comments: “Acronyms, initials and condensed words may be acceptable in otherwise appropriate terminology.”

I fancy that abiding by such rules may prove increasingly difficult as time rolls by. I wonder what steps might be taken to ease the tense situation.

Back to Top