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Binding properties of dipropyltryptamine at the human 5-HT1a receptor
Harish V Thiagaraj1, Ethan B Russo, Andrea Burnett
1Department of Biomedical and Pharmaceutical Sciences, The COBRE Center for Structural and Functional Neuroscience, School of Pharmacy and Allied Health Sciences, The University of Montana, Missoula, Montana 59812-1552, USA.
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.
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