The vast majority of drugs show a remarkably high correlation
of structure and specificity to produce pharmacological effects.
Experimental evidence indicates that drugs interact with receptor
sites localized in macromolecules which have protein-like properties
and specific three dimensional shapes. A minimum three point
attachment of a drug to a receptor site is required. In most
cases a rather specific chemical structure is required for the
receptor site and a complementary drug structure. Slight changes
in the molecular structure of the drug may drastically change
Several chemical forces may result in a temporary binding
of the drug to the receptor. Essentially any bond could be involved
with the drug-receptor interaction. Covalent bonds would be very
tight and practically irreversible. Since by definition the drug-receptor
interaction is reversible, covalent bond formation is rather
rare except in a rather toxic situation. Since many drugs contain
acid or amine functional groups which are ionized at physiological
pH, ionic bonds are formed by the attraction of opposite charges
in the receptor site.
Polar-polar interactions as in hydrogen bonding are a further
extension of the attraction of opposite charges. The drug-receptor
reaction is essentially an exchange of the hydrogen bond between
a drug molecule, surrounding water, and the receptor site.
Finally hydrophobic bonds are formed between non-polar hydrocarbon
groups on the drug and those in the receptor site. These bonds
are not very specific but the interactions do occur to exclude
water molecules. Repulsive forces which decrease the stability
of the drug-receptor interaction include repulsion of like charges
and steric hindrance. Steric hindrance refers to certain 3-dimensional
features where repulsion occurs between electron clouds, inflexible
chemical bonds, or bulky alkyl groups.