2-Aminoethylnitrate: earlier investigation as a drug was missed by recent authors due to changes in nomenclature

Drugs or compounds that are tested as potential drugs can be known by several different names. We have all scratched our heads a bit trying to chase a drug name through the literature. We now publish a letter drawing attention to a paper in BJP whose title starts off with ‘A new class of organic nitrates:’ (Schuhmacher et al., 2009) and which had an accompanying Commentary entitled ‘Aminoethyl nitrate – the novel super nitrate?’ (Bauersachs, 2009). The Letter writer, Miss Satvika Uppu, an undergraduate student at Louisiana State University, points out that this chemical, known by a different name, had been tested for such an effect fifty years ago (Batterman and Mouratoff, 1963).

We now publish her letter together with a response from the paper's authors. We will also publish their response as a correction to the paper.

As a Pharmacological journal, BJP's ‘Author Guidelines’ (http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1476-5381/homepage/ForAuthors.html) state that ‘Drug names should be International Non-proprietary Names (INN). See website http://mednet.who.int for a full list. If a drug has no INN, its full chemical name must be used (for nomenclature rules, see Handbook for Chemical Society Authors (London, Chemical Society – http://rsc.org) or its structural formula given’. This was all in order in the paper in question and a search in the RSC site does lead back to the old names. So the authors of the recent BJP paper should have found and mentioned the papers cited by Miss Uppu, but, as they explain, this was understandable.

The compound aminoethyl nitrate was investigated for its vasodilator and anti-anginal properties around 1960 and, particular formulations, was given two names: itramin tosylate or Nilatil (which was trademarked). In the light of this, the title of the paper ‘A new class of organic nitrates …’ seems inappropriate.

The reason that this early work was missed may relate to the fact that no one cited it. The original paper by Batterman and Mouratoff (1963) does not seem to have been cited at all, and the one by Kinnard et al. (1964) was cited once, by Fremont (1967), and that seems not to have been cited. However, Miss Uppu found them so it was possible! Alerted by her detective work, I found another couple of papers, one earlier (Ehrenberger, 1960), one later (Takenaka and Umeda, 1976), than the ones she found.

Of course, the recent paper in BJP provides new information on mechanisms of action. In the 1960s, there was little knowledge of the mechanism of action of nitrates. It was in the late 1970s that Furchgott and Zawadzki (1980) discovered that NO was released from vascular endothelium and that led to a great amount of work on the mechanisms of nitrates which donate NO. I am quite sure that there was no intention to deceive as Miss Uppu implies. We all miss things sometimes.