New putative selective agonists at the D-1 dopamine receptor: behavioural and neurochemical comparison of CY 208-243 with SK&F 101384 and SK&F 103243. 1990

A M Murray, and J L Waddington
Department of Clinical Pharmacology, Royal College of Surgeons, Dublin, Ireland.

Three putative D-1 agonists with nonbenzazepine structures were compared with the prototype benzazepine D-1 partial agonist SK&F 38393 for their behavioural effects in the intact adult rat, and for their relative affinities for D-1 and D-2 dopamine receptors in vitro. SK&F 103243, a restricted conformation analogue of SK&F 38393, and SK&F 101384 (8-Cl-ADTN) showed low affinity for D-1 and D-2 receptors in in vitro binding studies, and failed to induce any behavioural effects on peripheral administration. CY 208-243, an indolophenanthridine derivative, showed appreciable affinity not only for D-1 receptors but also for D-2 receptors, while in behavioural studies it showed some of the characteristics of a partial D-1 dopamine receptor agonist; thus, it failed to promote stereotyped behaviour, but induced episodes of intense grooming which were sensitive to blockade by the D-1 antagonist SCH 23390. No such effect was induced by the selective D-2 agonist RU 24213. CY 208-243 is the first nonbenzazepine which shows some of the properties of a D-1 agonist in the intact adult animal. However, the differences between its in vitro binding characteristics and its functional properties remain enigmatic.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297 Male Males
D009281 Naphthalenes Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D010617 Phenanthridines
D010627 Phenethylamines A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed) Phenylethylamines
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
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
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
D005449 Fluorenes A family of diphenylenemethane derivatives.

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