Thomas A. Ban: Psychopharmacology
Baltimore: Williams and Wilkins; 1969

Leon S. Morra’s Extracts - 3
Part One, Chapter One: General Principles
A.    Structure and Activity

            Chapter One is divided into three sections: A. Structure and Activity, B. From Chemical Synthesis to Clinical Application and C. Legal and Ethical Considerations. 

            “The first attempts to correlate chemical structure and biological activity” were made by Brown and Fraser in 1968 and by Blake in 1869, 1970 and 1984. It was “originally based on the assumption that some kind of chemical interaction occurred between a given drug and specific tissues by the organism...  It is now postulated that cell surfaces have a variety of receptor sites which can be occupied only by the appropriate activating drug, and it is a specific chemical-interaction which occurs between the drug and the cell receptor which is responsible for the characteristic pharmacological and biological actions.” An alternative theory is that the “rate of association of a drug with the cellular receptor in the brain and the speed of their dissociation which determine pharmacodynamics, and consequently, clinical effects.” It was also proposed that “the activity of some of the psychoactive compounds may be better understood in terms of ‘charge-transfer’ phenomena which is also referred to as ‘redux reaction’.”

            Structure-activity relationships were examined in the seven groups of psychoactive drugs in clinical use: 1. Barbiturates, 2. Amphetamines, 3. Phenothiazines, 4. Rauwolfias, 5. Tricyclic Antidepressants, 6. Monoamine Oxidase Inhibitors and 7. Benzodiazepines. It was concluded|: ”In spite of the various theoretical formulations, the work on structure-activity relationships is primarily  based on empirical observations. Irrespective of the numerous structure-activity correlations and relationships, the stage of development has not been reached, whereby the investigator can purposefully produce specific chemical and  physiochemical changes which can predictably induce psychotherapeutic or psychotomimetic effects.” 


Leon S. Morra

February 23, 2017