Central dopaminergic and 5-hydroxytryptaminergic effects of C3-methylated derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin

J Med Chem. 1988 Jun;31(6):1130-40. doi: 10.1021/jm00401a012.

Abstract

A number of stereochemically well defined C3-methylated derivatives of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been synthesized, and their stereochemical characteristics have been studies by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics calculations. The compounds were tested for activity at central 5-HT and dopamine (DA) receptors, by use of biochemical and behavioral tests in rats. In addition, the ability of the cis- and trans-8-hydroxy-3-methyl-2-(di-n-propylamino)tetralins (15 and 11) to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The stereoselectivity of the interaction of 11 and 15 with 5-HT receptors was much greater than that of 8-OH-DPAT. Observed rank order of potencies in the 5-HT1A binding assay corresponds to that in the in vivo biochemical assay.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Animals
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Methylation
  • Molecular Conformation
  • Naphthalenes / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Receptors, Serotonin / drug effects*
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / chemical synthesis
  • Tetrahydronaphthalenes / pharmacology*
  • X-Ray Diffraction

Substances

  • Naphthalenes
  • Receptors, Dopamine
  • Receptors, Serotonin
  • Tetrahydronaphthalenes
  • 8-Hydroxy-2-(di-n-propylamino)tetralin