Dopamine/serotonin receptor ligands, part III [1]: synthesis and biological activities of 7, 7'-alkylene-bis-6, 7, 8, 9, 14, 15-hexahydro-5H-benz[d]indolo[2, 3-g]azecines -- application of the bivalent ligand approach to a novel type of dopamine receptor antagonist

Arch Pharm (Weinheim). 2002 Aug;335(8):367-73. doi: 10.1002/1521-4184(200211)335:8<367::AID-ARDP367>3.0.CO;2-C.

Abstract

A series of 7, 7'-alkylene-bridged dimers(7a-e) of the benz [d]indolo[3, 2-f]azecine derivative LE300 was synthesized. Affinity and functional activity at dopamine D(1) and D(2) receptors were estimated by radioligand binding and a functional Ca(2+) assay. All the new bivalent ligands showed significant binding affinities to both D(1) and D(2) receptors with an optimal distance between the two monomeric recognition units of 6 methylene moieties. The D(1)/D(2)-selectivity pattern was dependent on the spacer length. No (7a, b) or only moderate (7c-e) functional activity was detected for all bivalent compounds by measuring the inhibition of agonist-induced increase in intracellular Ca(2+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Alkenes / chemical synthesis*
  • Alkenes / pharmacology*
  • Binding, Competitive / drug effects
  • Calcium / metabolism
  • Cell Line
  • Dopamine Antagonists / chemical synthesis*
  • Dopamine Antagonists / pharmacology*
  • Fluorescent Dyes
  • Humans
  • Indicators and Reagents
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Dopamine D2 / drug effects
  • Receptors, Serotonin / drug effects*

Substances

  • 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine
  • Alkenes
  • Dopamine Antagonists
  • Fluorescent Dyes
  • Indicators and Reagents
  • Indoles
  • Ligands
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Serotonin
  • Calcium