dopaminergic pharmacophore; ergot alkaloids; structure-activity relationships; drug design
The problem of defining structural similarities between apomorphine and certain ergot alkaloid derivatives, two chemically dissimilar types of drugs having similar pharmacological effects, is addressed by considering the three-dimensional geometry of the molecules. Conformational analytical concepts can be used to design new chemical entities and to assess structure-activity relationship hypotheses, and indeed this strategy has led to synthesis of new categories of potentially clinically valuable agents. Some conclusions are presented with respect to the combinations of atoms within the molecules in various chemical categories of dopaminergic agonists, which are responsible for the observed pharmacological effects. On the basis of these conclusions, some general properties of in vivo dopamine receptors are inferred, and proposals are advanced for structural analysis of the molecule of dopamine itself, which may be applicable to the design of new, superior therapeutic agents for those pathological conditions which are referable to the dopaminergic nervous system.
Proceedings of the Iowa Academy of Science
©1986 Iowa Academy of Science, Inc.
Cannon, Joseph G.
"The Design of Potential Anti-Parkinsonian Drugs: What is the Dopaminergic Pharmacophore in Ergot Alkaloids?,"
Proceedings of the Iowa Academy of Science, 93(4), 167-174.
Available at: https://scholarworks.uni.edu/pias/vol93/iss4/3