Structural determinants of selective affinity for brain D-1 dopamine receptors within a series of 1-phenyl-1H-3-benzazepine analogues of SK&F 38393 and SCH 23390. 1985

K M O'Boyle, and J L Waddington

A series of 1-phenyl-1H-3 benzazepine analogues of the D-1 agonist SK&F 38393 and of the D-1 antagonist SCH 23390 were compared for their relative abilities to displace the binding of [3H]piflutixol and [3H]spiperone to striatal D-1 and D-2 receptors respectively. The benzazepine analogues varied in substitutions at the 3- and 7-positions which distinguish SK & 38393 from SCH 23390. Substitutions at these positions critically influenced affinity for D-1 receptors over a 2000-fold range but influenced affinity for D-2 receptors over only a 30-fold range. 7-Substituents prominently increased affinity and selectivity for D-1 receptors with a rank order of Br = Cl much greater than CH3 greater than H greater than OH. 3-Methylation had a less marked and less selective action to increase affinity for D-1 receptors. Such structural relationships may aid the definition of the topography of brain D-1 receptors and the development of improved selective agents.

UI MeSH Term Description Entries
D008297 Male Males
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001067 Appetite Depressants Agents that are used to suppress appetite. Anorectic,Anorectic Agent,Anorectics,Anorexic Drug,Anorexigenic Drug,Appetite Depressant,Appetite Suppressant,Appetite Suppressants,Appetite-Depressing Drug,Appetite-Suppressant Drug,Anorectic Agents,Anorexic Drugs,Anorexigenic Drugs,Appetite-Depressing Drugs,Appetite-Suppressant Drugs,Agent, Anorectic,Agents, Anorectic,Appetite Depressing Drug,Appetite Depressing Drugs,Appetite Suppressant Drug,Appetite Suppressant Drugs,Depressant, Appetite,Depressants, Appetite,Drug, Anorexic,Drug, Anorexigenic,Drug, Appetite-Depressing,Drug, Appetite-Suppressant,Drugs, Anorexic,Drugs, Anorexigenic,Drugs, Appetite-Depressing,Drugs, Appetite-Suppressant,Suppressant, Appetite,Suppressants, Appetite
D001552 Benzazepines Compounds with BENZENE fused to AZEPINES.
D013134 Spiperone A spiro butyrophenone analog similar to HALOPERIDOL and other related compounds. It has been recommended in the treatment of SCHIZOPHRENIA. Spiroperidol,Spiroperone
D013892 Thioxanthenes Compounds with three aromatic rings in linear arrangement with a SULFUR in the center ring.

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