Conformity pharmacodynamic

The receptors for these hormones are typical seven-transmembrane-domain serpentine peptides (see Chapter 2 Drug Receptors Pharmacodynamics). Each hormone acts as a ligand within a receptor pocket, inducing conformational activating changes in the receptor. The conformational changes in the receptor s intracellular third loop and carboxyl terminal tail activate an adjacent intracellular G protein. The Gm protein is associated with the receptors for GnRH and TRH, G with the dopamine receptor, and Gs protein with the receptors for the other hormones listed above. 

The non-specific interaction of amlodipine with the membrane may thus lead to a defined and specific location, orientation, and conformation required for binding to a transmembrane receptor protein. It may help to understand and explain its pharmacodynamic and pharmacokinetic profile, which shows a slow onset and a long duration of activity compared with uncharged drugs of this class [95]. 

From these simple considerations it becomes clear that organic drugs and their sila-analogues may differ in their chemical (reactivity) and in their physicochemical properties (e.g. lipophilicity) as well as in their structure (shape and size, bonding geometries, conformational behavior). It can be expected that these chemical, physicochemical and structural sila-substitution effects may, in principle, result in biological sila-substitution effects—by influencing the pharmacodynamics and/or the pharmacokinetics. 

The question now arises, which has possibly a more direct pharmacodynamic significance, of what becomes of this conformational preference of the free zwitterionic GABA in solution. This section represents an attempt to answer it. 

---