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filesdownloads pc. He was thus. Although they had many of the systems, they are of no current use to us as M. of Textor considered the editors to be the key source of a continuous text.. Tm-heera-font-download downloaderThe present invention relates to substituted 1-(2-halopyridyloxy)indoles which selectively bind to brain dopamine receptor sites. It also relates to pharmaceutical compositions comprising such compounds and to methods of using such compounds to treat central nervous system disorders.
Dopamine receptors are subdivided into two broad categories: (1) DA.sub.1 receptors, which are characterized by agonist activity at the dopamine and adrenergic receptors and (2) DA.sub.2 receptors, which are characterized by antagonist activity at the dopamine and adrenergic receptors. Numerous physiological effects have been associated with interactions at the DA.sub.1 receptor sites in animals (for review see Jarvius, P. F. et al., “Central Dopaminergic Effects of Drugs: III. Comparative Characteristics of Dopamine Receptors,” Trends in Pharmacol. Sci., 11, 185, 1990). For example, these receptors have been associated with an array of motor and behavioral effects that are of use in the treatment of Alzheimer’s disease, Parkinson’s disease, Attention Deficit Hyperactivity Disorder, tardive dyskinesia, Tourette’s syndrome, endocrine disorders such as prolactin secretion and growth hormone regulation, vasopressin secretion, sexual behavior, feeding behavior, memory, mood, and cognition.
Toward developing drugs that are selective for the DA.sub.1 receptor subtype, Lazarenko, N. et al., “Selective Dopaminergic Agents: Synthesis and Pharmacological Activity of Some 1-(4-Substituted-1-piperazinyl)alkyl and 1-(4-Substituted-1-piperidinyl)alkyl-2,3-dihydro-1H-indoles,” Arzneim.-Forsch., 29, 1099-1113 (1979) reported that phenoxyethyl 1-(4-phenyl-1-piperidinyl)pyrrolidine showed selectivity for the DA.sub.1 receptor when tested in binding studies. However, this compound did not exhibit selectivity in functional assays.
Certain indolyloxyethylpiperidine and piperidine compounds