6-Substituted tricyclic partial ergoline compounds are selective and potent 5-hydroxytryptamine sub 1A receptor agents

Journal Article · Mon Jan 01 00:00:00 EST 1990 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(90)90197-Y· OSTI ID:6254314

Slaughter, J L; Harrington, M A; Peroutka, S J ^[1]

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1. Stanford Univ. School of Medicine, CA (USA)

A series of 6 tricyclic partial ergoline derivatives was analyzed using radioligand binding assays. Four agents (LY 178210, LY 254089, LY 197205, and LY 197206) display high affinity for 5-hydroxytryptamine{sub 1A} (5-HT{sub 1A}) receptor binding sites labeled by ({sup 3}H)8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and display {ge} 150 fold selectivity for the 5-HT{sub 1A} over the 5-HT{sub 1D} receptor binding site. The most potent agent investigated, LY 178210, is essentially inactive at a total of 12 other neurotransmitter receptor binding sites in the brain. Using a forskolin-stimulated adenylate cyclase assay as a model of 5-HT{sub 1A} receptor function, LY 178210 was found to display partial agonist activity which was blocked by 10{sup {minus}5} M ({minus})pindolol. These data indicate that LY 178210 is a potent and selective 5-HT{sub 1A} receptor partial agonist.

• OSTI ID: 6254314
• Journal Information: Life Sciences; (USA), Vol. 47:15; ISSN 0024-3205
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
SEROTONIN
RECEPTORS
SYMPATHOLYTICS
RADIOASSAY
AFFINITY
BIOCHEMICAL REACTION KINETICS
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TRACER TECHNIQUES
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REACTION KINETICS
SYMPATHOMIMETICS
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550201* - Biochemistry- Tracer Techniques