Binding properties of dipropyltryptamine at the human 5-HT1a receptor

Pharmacology. 2005 Jul;74(4):193-9. doi: 10.1159/000085649. Epub 2005 May 9.

Abstract

Dipropyltryptamine (DPT) is a synthetic indolealkylamine first characterized in the 1960s. Largely forgotten since the discovery of multiple serotonin receptor subtypes, some of the properties of DPT at the cloned human 5-HT1a receptor are described here. When [3H]8-OH-DPAT is bound to the receptor, DPT inhibits the interaction with an IC50 of 0.1 micromol/l. This interaction is shown to be competitive when double-reciprocal plots of the DPT/agonist interaction are analyzed. DPT's effects in the signal transduction system are complex. While DPT alone (0.1-1,000 micromol/l) activates Gi when both cAMP and gamma-S-GTP incorporation are measured, in the presence of 5-HT (0.1-10 micromol/l), DPT blocks the agonist effect. In combination, the findings suggest that DPT is a moderate affinity partial agonist at the human 5-HT1a receptor. These results provide evidence that DPT has potential as a versatile experimental tool at 5-HT1a receptors.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / metabolism
  • Animals
  • Binding, Competitive / drug effects
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Kinetics
  • Molecular Structure
  • Radioligand Assay
  • Receptor, Serotonin, 5-HT1A / genetics
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin / pharmacology
  • Sulfur Radioisotopes
  • Transfection
  • Tritium
  • Tryptamines / chemistry
  • Tryptamines / metabolism*
  • Tryptamines / pharmacology

Substances

  • Sulfur Radioisotopes
  • Tryptamines
  • Tritium
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • dipropyltryptamine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Cyclic AMP