2.11.1 Disease-Centered Receptor SelectionIn this approach, several possible receptors for a single disease entity (e.g., Alzheimer’s dis-
ease, stroke, rheumatoid arthritis) are explored. If the objective is Alzheimer’s disease, for
example, then drugs may be designed to target one or more of the following potential recep-
tor sites: acetylcholine esterase,β-amyloid peptide, or tau protein—each being a protein,
functionally and structurally distinct from one another, that may (or may not) play a central
role in the aetiology, pathogenesis, or symptomatology of Alzheimer’s disease. The strength
of a disease-centered approach is that it permits the designer to pursue whatever target is
necessary to fight the disease, without being confined to a particular class of receptor.
2.11.2 Systems-Centered Receptor SelectionPhysiologically, the human body may be considered as a collection of various functional
systems: nervous, endocrine, immune, cardiac, respiratory, gastrointestinal, genitourinary,
musculoskeletal, and dermatological. These physiological systems may be categorized
into three larger groupings: control systems (nervous, endocrine, immune), support
RECEPTORS: STRUCTURE AND PROPERTIES 97Figure 2.6 Second messenger systems mediate effects of drugs acting on G-protein coupled
receptors. The drug stimulates an enzyme upon binding to the membrane-bound receptor. If the
enzyme is adenylate cyclase, this stimulates the production of cyclic AMP, which in turn stimulates
protein kinase A, causing protein phosphorylation and ultimately a biological response. If the
enzyme is phospholipase C, this stimulates the production of the phosphoinositide cycle, which in
turn stimulates two mechanisms: (i) increased protein phosphorylation via stimulation of protein
kinase C by diacylglycerol (DG); and (ii) the activation of calcium-regulated cellular systems.
(Adapted from D. G. Grahame-Smith, J. K. Aronson (2002). Clinical Pharmacology and Drug
Therapy, 3rd Edn. New York: Oxford University Press. With permission.)