VERY serious student of medicine well knows

E that his vocabulary must cularge during the

course of his schooling to include, with respect to human anatomy alone, the names of some 200 bones, hundreds of nerves, muscles, and vessels, and dozens of organs. Quite providently, evolution proceeds slowly enough for this store of information to remain fairly fixed and constant for the student of any given generation. This is not so, however, for the host of drugs which he must learn to know by name, to say nothing of identity, action, and use.

What perplexes students and practicing physicians alike is why these drugs must be known by seldom fewer than 3, usually 4, and often more than a half-dozen different names. And those who go abroad for study find themselves obliged to learn still other names in use there for familiar drugs. These comments explore this baffling situation and will perhaps dispel some common misunderstandings, especially with respect to nonproprietary

names.

The Five Categories of Drug Names

On its way to a place in therapeutics, a medicinal compound acquires names or designations that fall into 5 categories. When first synthesized, or when first identified if derived from a natural source, a potentially useful compound receives a systematic chemical name. To be adequate and fully specific, this name must reveal every part of the compound's molecule, including any and all forms of isomerism if present, and must be such that it can describe only the compound concerned and no other. The systematic chemical name is generally so formidable that even chemists, especially those concerned with the synthesis of organic medicinal compounds, have little patience with it and tend to coin "trivial" names to abbreviate the names for specific compounds or groupings. Although examples of trivial names are numerous, citing one suffices to illustrate the advantages of their use. Chemically, phenol is hydroxybenzene or hydroxycyclohexatriene; yet how many recognize at once that the "trivial" name and the 2 systematic names are synonymous?

Rather interesting stories lie behind the selection of some trivial names, as in the case of barbituric acid. This was the discovery of the chemist, Baeyer, who came upon the new compound as a combination of maleic acid with a breakdown product of Director of Revision, U. S. Pharmacopeia.

The multiplicity of names for drugs is inevitable. In addition to the systematic chemical name for a given drug there are the trivial names by which it may be known familiarly among chemists, the code number needed during research and development, the proprietary names needed when the drug is sold, and the generic name that is used as the common designation for all the various brands. The generic name, which is nonpropric tary, is usually chosen by concerted action of representatives of manufacturing, medical, and governmental organizations. The medical professio. could cooperate in the effort to minimize confusion by using accepted nonproprietary names.

uric acid. He wrote later that he was enamoured at the moment of a charming lady named Barbara, and so he decided to call the new compound "barbituric acid" in her honor. The story does not end there, for later the physician von Mehring took a trip to Italy shortly after discovering the hypnotic properties of diethylbarbituric acid, and, as he approached the city of Verona, he was struck with the idea of naming this compound Veronal. But for the development of newer barbiturates, this name would still be in use as a brand name for diethylbarbituric acid.

For the same reasons that chemists turn to trivial names as a shorthand form of chemical designation, their colleagues, the pharmacologists and others, often identify new compounds during their study in the laboratory by code numbers, which are usually preceded by a common prefix distinctive of the laboratory in which the work is being done. This logical practice probably antedates Ehrlich, who, however, made it famous about 50 years ago when he numbered the compounds during his search for the "magic bullet" to cure syphilis. Thus, his compound 606 is probably better known by number than by the name arsphenamine or Salvarsan. Recently, another laboratory code number, MER/29. became so well known that it was adopted as the registered trademark for the anticholesterolemic drug concerned (triparanol). If used, a compound's code number stays with it through the laboratory study and frequently through the clinical investiga

tion. While there is little need to identify the code number with the respective chemical name of the compound in the earlier stages, there is good reason for having it call to mind the laboratory that employs it. (This point is treated more fully in a subsequent section.) When used in scientific publications, the code number must be suitably identified as a matter of scientific specificity.

When tests show that the compound has real utility for therapeutic purposes and the investigation justifies offering it for sale, a proprietary name is needed. Known also as the trademark, since it is. registered as such with the United States Patent Office, this name identifies the specific brand of the compound with the firm that owns the mark. As a rule, this is the firm that has borne the expense of synthesizing the compound (which finally may now be called a drug) and of carrying out the laboratory and clinical tests, to say nothing of bearing the cost of producing it in sufficient quantities for wide distribution and making its virtues known to physicians. This proprietary name is therefore the exclusive, and ofttimes very valuable, property of the firm with which it is identified. It is incorrect to speak of it as the "trade name" which, under trademark law, is synonymous with the company name.

At this stage there also appears the generic or nonproprietary name. These two terms are regarded as synonymous, yet they differ in ways that Stecher' has clearly distinguished:

The adjective generic obviously comes from the Latin word genus and suggests classification into genera as is the practice in botany and zoology. Actually the term is a misnomer as used in the drug field. The generic name does not relate to a class or genus of drugs; it denotes a single drug. Generic here is taken as opposed to specific. Specific applies to the trademark (also called brand or proprietary name) which is specific to one sole owner, while the generic name is nonproprietary. The term nonproprietary is more accurate and descriptive, but generic sounds better, is shorter and easier to pronounce-and so will probably stay with us for a long time to come, although it is a contradictory term. It most decidedly does not describe a genus or kind of products common to all the pharmaceutical trade. It does denote or should denote a unique substance definable in chemical nomenclature as a single chemical compound not to be confused with any other substance of the same kind or belonging in the same group of drugs. This definition has been broadened to allow the coining of generic names for natural aggregates of substances such as extracts of plant or animal origin, but. excludes proprietary mixtures where each component has its own generic name.

Not only is the term "generic" misapplied, but actually it is needed in drug nomenclature in its true meaning, i.e., as a designation for families of active compounds. Thus, vitamin A is the true generic name for a family of at least 4 closely related compounds having vitamin A activity. Similarly, vitamin D and vitamin B12 are true generic names for the families of vitamin D compounds and vitamin B12 compounds.

But the term "generic" has recently acquired an economic aura or aroma, depending upon the point

of view, that rather spoils its utility for designating a class of drug names. Actually, by curious accident, a new and appropriate usage of "generic" has sprung up in the sense that today it is used to designate collectively the several brands of a given drug that are marketed by several firms; that is, the various brands of a single drug may be regarded as a family or genus of products, and their respective nonproprietary names are "generic" as a group. However, the term "nonproprietary" deserves adoption until something more suitable is proposed, because its specificity outweighs its unwieldiness.

One final class of names remaining to be discussed consists of the official titles used in the U. S. Pharmacopeia and the National Formulary. With rare exceptions, these are the nonproprietary names that have been used during the period of establishing the drug's place in rational therapy. An example of the kind of changes made by the U.S.P. Committee of Revision is the U.S.P. title Chlorpheniramine Maleate, which represents a slight condensation of the longer nonproprietary name chlorprophenpyridamine maleate. The latter name was in use for some time before the drug was recognized in the Pharmacopeia.

At this time, proposals are pending before Congress (H.R. 6245 and S. 1552) to make the Food and Drug Administration responsible for selecting nonproprietary ("official") names for drugs and for reviewing periodically U.S.P. and N.F. titles with a view to changing them "in the interest of simplicity and usefulness." While there is little on which to base a prediction on how such a law would operate if enacted, sound arguments can be marshalled for the view that no new law is needed, at least not until some use has been made of the present law to accomplish the desired end. It is patently clear that only a little cooperation on the part of all concerned would bring about marked improvement. It would seem that much would be accomplished if the Food and Drug Administration simply required, as a matter of safety, that the labeling of all new drugs subject to New Drug Applications should employ either the U.S.P. or N.F. name, if there is one, or ascertain what "common or usual name" has been established and require that it be used. Wilson* notes several cases in which 2 or more names have been used for a single drug.

Finally, with respect to the review, the record of the past supports 2 statements with considerable certainty. First, experience has shown that changes in U.S.P. or N.F. titles cause so much confusion that it is unlikely that the Food and Drug Administration would suggest much, if any, alteration in existing titles. Second, the proposed system were to be put into operation, it is quite unlikely that either the U.S.P. or N.F. Committees of Revision would select titles that differed from those chosen by the Food and Drug Administration. This is not to say that the U.S.P. Committee of Revision

has approved all titles chosen by a government agency in the past, since the Committee considered some of the names assigned to biological products by the National Institutes of Health unsuitable for U.S.P. titles. Two examples of the few cases in which the U.S.P. title differs from the N.I.H. name (the former listed first) are: Human Blood Cells vs. Packed Red Blood Cells (Human) and Normal Human Serum Albumin vs. Normal Serum Albumin (Human).

The Need for Nonproprietary Names

Not all therapeutic agents are the object of multiple naming. Those that are common household chemicals generally have the fewest names, yet the common and simple substance "sugar" is listed in the Pharmacopeia as “sucrose," and, as a 12-carbon disaccharide, it has a rather formidable chemical name. Perhaps no compound has simpler nomenclature than U.S.P. Sodium Chloride, which has long been known simply as "salt." Here is an instance where an ancient name of a single com. pound was appropriated as a truly generic name for a large chemical class of compounds known as salts. Various brands of sodium chloride are sold as "... Brand of Tablet Salt."

In cases in which the same medicinal compound is available from a considerable number of firms, as in the case of isoniazid, a really complex situation exists. The drug is well known also by its trivial chemical name, isonicotinic acid hydrazide. At one time, this.tuberculostatic drug was available from as many as 25 different firms, almost all of which had coined their own brand names, but isoniazid, the U.S.P. title, was the one name in common for all the various brands. Therefore, if for no other reason than as a common bond of identity in the market place, nonproprietary names are needed.

But there is another reason, much more cogent from a manufacturer's standpoint, in that nonproprietary names serve to protect trademarks. The federal law governing the granting and use of trademarks, the Lanham Act of 1946, provides that a trademark may fall into the public domain if the public adopts it as a common name. Years ago, trademark rights to the name aspirin were lost in the United States; anyone can use it here, although proprietary rights to it are still valid in some other countries.

It must be pointed out that nonproprietary names are considered only for single compounds, whether of synthetic or natural origin. While trademarks can be assigned to mixtures, only the active ingredients of such mixtures are designated by nonproprietary names.

Desirable Attributes in Nonproprietary Names Judgment on the suitability of a nonproprietary name depends entirely on the judge's point of view. Taking the viewpoint of the manufacturer, the

name need be only adequate to protect his trademark; he has no real concern about length and unwieldiness since, once a nonproprietary name is made available, only due diligence is demanded of him to protect his trademark. This he does by using a symbol, an encircled superscript R or its equivalent, and by taking pains always to warn editors and authors who fail to follow the convention of capitalizing the initial letter of a trademark or otherwise fail to show its protected status. Diligence in this respect can offset the tendency to substitute the trademark for an impossibly unwieldy nonproprietary name.

Freedom from conflict with any other names used for drugs is an important attribute, and the manufacturer takes pains to ascertain that the nonproprietary name, as well as his trademark, passes this test. A complaint of possible conflict gave rise to the change in pronunciation of Banthone indicated by the long "i"; the same might have been achieved by substituting a "y" but this seems not to have been considered. The manufacturer expects others to be equally painstaking, but bitter court battles have arisen when, for one reason or another, the rules of the game have been transgressed. This factor works strongly against the choice of short nonproprietary names, for the risk of conflict diminishes with length; and a long name may incorporate several syllables, any one of which taken alone would cause protest. The viewpoint of the physician, pharmacist, teacher, and general public is often neglected in debating the suitability of nonproprietary names. Since the public scarcely has an advocate to plead its case, protests from those who fear injury from conflict may weigh disproportionately heavy in the balance.

Without entering into debate on the merits of prescribing exclusively by "generic" or nonproprietary names, it is self-evident that the convenience of all is served best when the nonproprietary names are as short and pronounceable as possible. Yet there is equal agreement on the proposition that the name should point up such relationships as exist among compounds that fall into a common pharmacological group. This mitigates against brevity and, indeed, leads directly to names that have been criticized for their length. Such is the case of the group of antibiotics, the parent member of which was named tetracycline. Adoption of that name logically led to the already known chlortetracycline and oxytetracycline, both available as the hydrochloride salt. There followed, as a result of commendable research. rolitetracycline, a pyrrolidine derivative, and demethylchlortetracycline, by the removal of a methyl group from chlortetracycline. Syllable-counters have a heyday with the hydrochloride of demethylchlortetracycline particularly; yet it fits logically into the pattern of the first names chosen. In retrospect, it might have helped to have picked tecline, or tycline, or some other available

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