Mechanisms of Drug Action

☆THE CHEMISTRY OF DRUG–RECEPTOR BINDING ፦     

⇨Biological receptors are capable of combining with drugs in a number of ways, and the forces that attract the drug to its receptor must be sufficiently strong and long-lasting to permit the initiation of the sequence of events that ends with the biological response. Those forces are chemical bonds, and a number of types of bonds participate in the formation of the initial drug–receptor complex.

⇨The bond formed when two atoms share a pair of electrons is called a covalent bond. It possesses a bond energy of approximately 100 kcal/mole and therefore is strong and stable; that is, it is essentially irreversible at body temperature. Covalent bonds are responsible for the stability of most organic molecules and can be broken only if sufficient energy is added or if a catalytic agent that can facilitate bond disruption,such as an enzyme,is present.Since bonds of this type are so stable at physiological temperatures, the binding of a drug to a receptor through covalent bond formation would result in the formation of a long-lasting complex. 

⇨The formation of an ionic bond results from the electrostatic attraction that occurs between oppositely charged ions.The strength of this bond is considerably less (5 kcal/mole) than that of the covalent bond and diminishes in proportion to the square of the distance between the ionic species.Most macromolecular receptors have a number of ionizable groups at physiological pH (e.g., carboxyl, hydroxyl, phosphoryl, amino) that are available for interaction with an ionizable drug.