Another drug is placed under international control
Pages: 20 to 22
Creation Date: 1952/01/01
The international conventions on narcotics provide means whereby control can be applied to substances that were unknown or not in use at the time those instruments were concluded. Thus, article 10 of the 19 February 1925 Convention makes it possible to place under control any narcotic drug to which the Convention does not apply, if the World Health Organization establishes that it is liable to be abused in the same way as the drugs covered by the Convention and to produce similar ill effects.
Article 11 of the 13 July 1931 Convention for limiting the manufacture and regulating the distribution of narcotic drugs, foresees a special procedure for submitting to the control any product obtained from any of the phenanthrene alkaloids of opium or from the ecgonine alkaloids of the coca leaf not in use at the time the Convention was signed for medical or scientific purposes.
But, whereas the control foreseen by the 1925 Convention has only a restricted scope and is subject besides to the acceptance, by the contracting Parties, of the World Health Organization recommendation on the drug concerned, the control established by the 1931 Convention is more strict and has to be applied automatically by all contracting Parties on reception of the notification from the Secretary-General of the United Nations.
Those synthetic narcotics which are not covered by the 1931 Convention can however be placed under the control provided by that instrument, through the application of the procedure set up by the Paris Protocol of 19 November 1948.
The Parties to that Protocol shall, upon receiving the communication from the Secretary-General notifying the decision of the World Health Organization, apply to the new drug the appropriate régime foreseen by the 1931 Convention. However, since the Protocol has so far been ratified by only thirty-seven States, application of that instrument is thereby limited to that number of States, whereas the control applied to a drug by virtue of the 1931 Convention, which has been ratified by more than sixty States, has consequently a much more general scope.
Recently, the provisions of the 1931 Convention were applied to a product manufactured in France and known by the name of "β-4-morpholinylethylmorphine". The procedure was started in September 1949 when the French Government addressed a notification to the Secretary-General asking that article 11 of the 1931 Convention be applied to the substance mentioned above, and in particular that it be considered as belonging to Group II.
According to the provisions of this article, any government authorizing trade in or manufacture for trade of any product obtained from any of the phenanthrene alkaloids of opium or of the ecgonine alkaloids of the coca leaf, not in use for medical or scientific purposes at the time the Convention was concluded, shall immediately notify the Secretary-General of the United Nations, who shall advise the other High Contracting Parties to the Convention and the World Health Organization. The latter, acting on the advice of a Committee of Experts appointed by the World Health Organization, will thereupon decide whether the product in question is capable of producing addiction or is convertible into such a drug. In the first case, that product is considered as one of the drugs mentioned in the Convention under Group I. In the second case, the question is submitted to a body of three experts who determine whether the product falls under sub-group ( b) of Group I or under Group II. Two of those experts shall be appointed by the Government concerned and by the Commission on Narcotic Drugs respectively, and the third expert by the other two. It must be explained that the Convention sets up a different control for the drugs in Group I and for those in Group II, this control being stricter for the drugs under Group I. Until a decision is arrived at concerning the definitive classification of the product under consideration, the Government concerned, unless it determines that this product is not capable of producing addiction or of conversion into a product capable of producing addiction, shall be bound to limit its fabrication to quantities not exceeding the total of the domestic requirements of the country for medical or scientific needs, and the quantity required for export orders; it shall also apply to this product the provisions of the 1931 Convention. The Conference which adopted the 1931 Convention considered that in this instance it is the régime provided for the drugs under Group I that must be applied.
At the same time as the notification addressed to the Secretary-General, the Ministry of Public Healths and Population of the French Republic transmitted a Note in which it was indicated that the product under consideration is marketed by the Dausse Laboratories in Paris, as a proprietary drug under the name of "hibernyl" which is offered:
As a syrup containing 0 gr. 10 phenylacetate of morpholinylethylmorphine per 100 gr. of syrup
In tablets containing 0 gr. 015 of morpholinylethylmorphine phenylacetate per tablet.
This note ended up with the remark that "in view of its low toxicity (three times less than that of codeine), its effectiveness (always equal to and frequently greater than that of codeine), and its lack of untoward side-effects, morpholinylethylmorphine constitutes a noteworthy therapeutic advance on codeine". The Dausse Laboratories received the authorization, pursuant to international conventions and to French regulations, to manufacture and market this product under licence.
The Secretary-General transmitted the notification from the French Government to the other governments Parties to the 1931 Convention as well as to the World Health Organization. The latter entrusted its Committee of Experts on Drugs Liable to Produce Addiction with the task of looking into the French request. This Committee, on the basis of the available documentation, was of opinion that there was insufficient evidence to permit a decision on the addiction-producing properties of morpholinylethylmorphine although it must probably be convertible to morphine and that, in any case, as an ether-oxyde of morphine, that substance was by definition in sub-group ( b) of Group I of the 1931 Convention.
When the Commission on Narcotic Drugs, at its fifth session in December 1950, considered the report of the Expert Committee (of WHO) on its second session, and particularly the item dealing with morpholinylethylmorphine, the French representative requested that the committee of three experts, provided for in paragraph 4 of article 11 of the Convention should be set up. This proposal gave rise to an exchange of views and the opinion was expressed then that the fact of classifying automatically morpholinylethylmorphine under sub-group ( b) might give rise to objections since codeine, another ether of morphine, was placed under Group II. The Commission finally decided to request the Secretary-General to invite the World Health Organization to re-examine the question in the light of fresh information which the French Government might make available.
The World Health Organization studied the supplementary documentation put at its disposal by France and transmitted to the Secretary-General, in February 1952, the text of the new findings formulated by its Committee of Experts. In the terms of this finding, " β-4-morpholinylethylmorphine" is not more liable than codeine to produce addiction and is therefore not assimilable to the drugs mentioned in sub-group ( a) of Group I; on the other hand it is less readily convertible than codeine to an addiction-producing drug and is, in consequence, assimilable to the drugs under Group II.
This finding was brought to the knowledge of governments by a Note from the Secretary-General of the United Nations which pointed out that the World Health Organization had, in fact, decided that, without being a drug liable to produce addiction, morpholinylethylmorphine could be transformed in such a drug. The Secretary-General, therefore, drew attention to provisions of paragraph 4 of article 11 which provide for the constitution of a body of three experts.
The Commission on Narcotic Drugs itself, at its seventh session in April and May 1952, took note of the findings of the World Health Organization in the matter and in view of the substance of these findings decided to appoint one of the members of the body of three experts, i.e., Mr. A. Kruysse, representative of the Netherlands. At the same time, the French Government advised the Secretary-General that it had appointed Mr. Charles Vaille, representative of France on the Commission on Narcotic Drugs to serve on this three experts' committee. Messrs. Kruysse and Vaille in their turn designated as third expert Mr. P. O. Wolff, Chief of the Section of Drugs Liable to Produce Addiction (World Health Organization), who was representing that Organization at the seventh session of the Commission on Narcotic Drugs. The three experts met during the session of the Commission and, after having elected Mr. Wolff President of the committee, they decided that " β-4-morpholinylethylmorphine" should be placed under the regime of control which applies to drugs included in Group II. They transmitted this decision to the Secretary-General of the United Nations who communicated it to the governments in accordance with the provisions of article 11, paragraph 5.
It should be mentioned that it is the first time since the Convention of 1931 came into force that the procedure provided for by article 11, paragraph 4, has been applied.
The swiftness with which the Commission on Narcotic Drugs, as well as the three experts designated to sit on the committee, acted made it possible to close without delay the procedure followed to give effect to the initial request of the French Government. The length of this procedure at its early stage was due to the necessity of taking into account the various technical and legal aspects of the problem under consideration.
"Preparations exempted from the control measures of the Narcotic Conventions" Bulletin on Narcotics, Vol. III, No. 4, October 1951.
The following preparations should be deleted from the list of those exempted from the control measures:
36. Sterilized solutions of morphine and atropine (page 6).
51. Sterilized solutions of eucodal and atropine (page 8).
The exemptions given these preparations by the Health Committee of the League of Nations were later rescinded by the same Committee (C.426.M.218.1935. III). This decision was notified to governments in circular letter C.L.162.1936.XI, but the letter made no mention of the necessity of correcting the "Recapitulatory List" (C.114.M.54.1932.III).
In formula 22, Suppositoria Plumbi composita, the amount of lead acetate, in powder, should be 2.4 grammes, not 12.4 grammes (page 5).
In the same issue, in the paper "Note on the total synthesis of morphine", p. 34-35, formula V should read:
(1) instead of β-thebainone, β-dihydrothebainone;3
(2) instead of the double bond on the right-hand ring, there should be a single bond.