Dopamine Receptor Subtype-Selective Drugs: D1-Like Receptors

Abstract

A survey is presented of the development of dopamine D-1 receptor-selective drugs, including agonists and antagonists. It is noted that there are presently no ligands that are specific for the D-1 vs the D-5 receptor isoforms. A general discussion is presented on the structure activity features of D-1/D-5 selective agents, with the conclusions developed that all known full D-1 agonists must contain a catechol moiety and, in addition, require the presence of a hydrophobic moiety (typically a phenyl ring) in the region adjacent to the beta side chain carbon of the embedded dopamine fragment. This latter structural feature is so crucial that when added to a noncatechol ergoline it gave a D-1-selective partial agonist. Present evidence indicates that D-1 agonists may be therapeutically useful in the treatment of Parkinson's disease, as well as improving cognition and working memory in schizophrenia and age-related cognitive decline. No D-1 agonist has yet been commercialized, and that seems largely due to the difficulties of oral bioavailability for catechol-containing drugs. PU - HUMANA PRESS INC PI - TOTOWA PA - 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA