2.11.1 Disease-Centered Receptor Selection
In this approach, several possible receptors for a single disease entity (e.g., Alzheimer’s disease, 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 receptor 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 Selection
Physiologically, 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
97
Figure 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.)
In this approach, several possible receptors for a single disease entity (e.g., Alzheimer’s disease, 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 receptor 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 Selection
Physiologically, 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
97
Figure 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.)