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    Synthetic Analgesics: Diphenylpropylamines
    Synthetic Analgesics: Diphenylpropylamines
    Synthetic Analgesics: Diphenylpropylamines
    Ebook217 pages1 hour

    Synthetic Analgesics: Diphenylpropylamines

    By Paul A. J. Janssen

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    Synthetic Analgesics, Part I: Diphenylpropylamines deals with the methods of synthesis, the physical and chemical properties, and the ""analgesic"" activity of diphenylpropylamines. Topics covered include the ""analgesic"" activity of methadone, morphine, pethidine, and codeine in animals; diamines and derivatives; R875 and related basic tertiary amides; esters derived from amino acids and secondary and tertiary alcohols; and ketimines, acyl ketimines, and ketones. This book is comprised of 21 chapters and begins with a brief background on the first chemical and pharmacological experiments on diphenylpropylamines, followed by a discussion on ""analgesic"" activity in humans and animals. The ""analgesic"" activity of methadone, morphine, pethidine, and codeine in animals is considered. The following chapters explore a variety of compounds such as 3:3-diphenylpropylamines, tertiary alcohols, secondary alcohols, primary alcohols, nitriles, diamines and derivatives, primary and secondary amides, acids and acid chlorides, and aldehydes. Sulfones, dissociation constants, and configurational studies are also described. This monograph will be a useful resource for researchers and practitioners in the fields of organic chemistry, analytical chemistry, and pharmacology.
    LanguageEnglish
    PublisherElsevier Science
    Release dateApr 24, 2014
    ISBN9781483152172
    Synthetic Analgesics: Diphenylpropylamines

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      Synthetic Analgesics - Paul A. J. Janssen

      laboratory.

      CHAPTER I

      Analgesic Activity in Man and in Animals

      Publisher Summary

      Analgesics are the compounds that are capable of relieving pain. In man, pain can be evoked by various noxious stimuli, such as heat, pressure, chemicals, and electric current. In view of the fact that pain is, by definition, a subjective sensation of mankind, it can only be studied in humans. Numerous ingenious means of inflicting pain that is quantifiable in mechanical, thermal, electrical, or chemical units of measurement have been devised. However, the main difficulty in interpreting the various results obtained by different authors originates from the fact that the reproducibility and standardization of the methods is a neglected problem. The first requirement for an ideal pharmacological method is that it should be reproducible by every investigator who follows exactly the directions given in a description of the method. To find out whether such descriptions exist at all, the whole problem of the standardization of pharmacological methods should be investigated by collaborative experimentation in many laboratories.

      A compound is said to possess analgesic activity when it is capable of relieving pain. Pain, of course, is a universal subjective experience of mankind, and everybody knows what is meant by it (39). Hence there is no point in trying to define this basic concept.

      In man, pain can be evoked by various noxious stimuli, such as heat, pressure, chemicals, electric current, etc. When such stimuli are applied to animals, their behaviour changes in a typical way. Generally speaking the animal either tries to avoid the stimulus by various flight reactions or, when flight is made impossible, it shows a series of reflexes, which are often interpreted as signs of discomfort. In man, the evidence on whether or not pain is relieved, is entirely based on the statement of the subject as expressed in the interview made by the observer. The nature of such statements, however, depends on several factors in constant operation, such as the willingness of the subject to talk about his feelings, the attitude of the observer towards the subject, the influence of the environment on the subject, his immediate problems, his hope or desperation and many other factors.

      Obviously, therefore, the study of the influence of one single factor, such as the administration of a drug, on the statements of a given subject necessitates special techniques. The elimination of bias on the part of the subject or the observer emerges clearly as a basic and essential requirement for such studies (39). Recently, the various problems concerning the measurement of pain and relief of pain were adequately reviewed by Beecher (39).

      In view of the fact that pain is, by definition, a subjective sensation of mankind, it can, strictly speaking, only be studied in humans. What we are able to study in animals is not pain itself, but the behaviour of the animal following a stimulus which provokes pain in man and also, of course, the influence of a given factor, such as the administration of a certain drug on the reactions of the animal. Rather full fists of references to the methods of producing pain for experimental purposes are given by Beecher (39) and O. Schaumann(402). Numerous ingenious means of inflicting pain which is quantifiable in mechanical, thermal, electrical or chemical units of measurement have been

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