Rational design of drugs implies the ability to predict the appropriate molecular structure of a drug on the basis of information about its biologic receptor. Until recently, no receptor was known in sufficient detail to permit such drug design. Instead, drugs were developed through random testing of chemicals or modification of drugs already known to have some effect. However, the characterization of many receptors during the past three decades has changed this picture. A few drugs now in use were developed through molecular design based on knowledge of the three-dimensional structure of the receptor site. Computer programs are now available that can iteratively optimize drug structures to fit known receptors. As more becomes known about receptor structure, rational drug design will become more common.
The spectacular success of newer, more efficient ways to identify and characterize receptors (see Chapter 2) has resulted in a variety of differing, and sometimes confusing, systems for naming them. This in turn has led to a number of suggestions regarding more rational methods of naming receptors. The interested reader is referred for details to the efforts of the International Union of Pharmacology (IUPHAR) Committee on Receptor Nomenclature and Drug Classification (reported in various issues of Pharmacological Reviews and elsewhere) and to Alexander SP et al: The Concise Guide to PHARMACOLOGY 2015/16: Overview.
CHAPTER 1 Introduction: The Nature of Drugs & Drug Development & Regulation
Br J Pharmacol 2015;172:5729. The chapters in this book mainly use these sources for naming receptors.
The interactions between a drug and the body are conveniently divided into two classes. The actions of the drug on the body are termed pharmacodynamic processes (Figure 1–1); the principles of pharmacodynamics are presented in greater detail in Chapter 2. These properties determine the group in which the drug is classified, and they play the major role in deciding whether that group is appropriate therapy for a particular symptom or disease. The actions of the body on the drug are called pharmacokinetic processes and are described in Chapters 3 and 4. Pharmacokinetic processes govern the absorption, distribution, and elimination of drugs and are of great practical importance in the choice and administration of a particular drug for a particular patient, eg, a patient with impaired renal function. The following paragraphs provide a brief introduction to pharmacodynamics and pharmacokinetics.
Most drugs must bind to a receptor to bring about an effect. However, at the cellular level, drug binding is only the first in a sequence of steps: + R → D-R complex → activation of coupling molecule → effector molecule → effect of metabolism of endogenous activator → increased activator action on an effector molecule → increased effect
Note that the final change in function is accomplished by an effector mechanism. The effector may be part of the receptor molecule or may be a separate molecule. A very large number of receptors communicate with their effectors through coupling molecules, as described in Chapter 2.
A. Types of Drug-Receptor Interactions