To Bond or Not to Bond: Chemical versus Physical Theories of Drug Action

of Michigan, published an article in the Journal of the American Medical Association entitled " The Pharmacologic Action of Drugs: Is It Determined by Chemical Structure or by Physical Characters? " 1 To a chemist today, this question might seem odd. The physical properties of a drug and its chemical structure are, after all, intimately related, and even if one wants to distinguish between closely integrated physical and chemical properties, surely both are involved in drug action. Physical properties such as solubility and chemical reactivity due to the presence of certain molecular structures can and do both influence pharmacological effects. At the turn of the twentieth century, however, the understanding of the nature of chemical bonding and of cellular structure and function was still in its infancy, and many chemists and pharmacologists sought a simplified answer to Cushny's question. There was thus significant controversy over whether the physical or the chemical properties of a substance could best explain its pharmacological action, and over the value of attempts to relate the physiological activity of a drug to its chemical structure. The fact that drugs may exert a selective action on specific organs of the body had long been recognized empirically and expressed vaguely in the traditional designation of certain remedies as cordials (acting on the heart), hepatics (acting on the liver), etc. 2 As early as the seventeenth century, the noted chemist Robert Boyle had tried to explain the specific effects of