Activity of Parthenolide at 5HT_2AReceptors

Abstract

Parthenolide displaces [3H]ketanserin from 5HT2A receptors from rat and rabbit brain and cloned 5HT2A receptors. Ki's are in the 100-250 microM range. These results suggest that parthenolide may be a low-affinity antagonist at 5HT receptors; it is unlikely that the entire mechanism of action can be explained by its modest 5HT2A receptor affinity.

Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice

“…Additionally, the relationship between 5-HT 2A and the closely related 5-HT 2C receptor densities in cortex and frontal cortex was examined. Whole Fone et al 1998;Hoyer et al 1985Hoyer et al , 1986Hulihan-Giblin et al 1994;Leonhardt et al 1992;Pranzatelli andBalletti 1992 b Schindler et al, unpublished c Hoyer et al 1985;Leonhardt et al 1992;Pazos et al 1985;Pranzatelli and Balletti 1992 d Battaglia et al 1983Battaglia et al , 1984Bonhaus et al 1995;Hagen et al 1994;Johnson et al 1996;Leonhardt et al 1992;Leysen et al 1982Leysen et al , 1988Lyon et al 1987;Meltzer et al 1989;Neale et al 1987;Nelson et al 1993;Pazos et al 1984;Rinaldi-Carmona et al 1992;Roth et al 1992;Sadzot et al 1989;Schotte et al 1983;Schreiber et al 1995;Wainscott et al 1996 c Aloyo andHarvey 2000, Schindler et al, unpublished;Weber et al 1997 d Bonhaus et al 1995;Hagen et al 1994;López-Giménez et al 1998;Nelson et al 1993;Pazos et al 1984;Sadzot et al 1989;Schotte et al 1983 -Giménez et al 2002), respectively. In addition to similarities to autoradiography results, the number of DOI-elicited HTRs in C57BL/6N mice in t...…”

Binding Properties of Dipropyltryptamine at the Human 5-HT1a Receptor

“…These conclusions have implications for use of DPT or structural analogues at the ligand-binding site of H5-HT1aR [21] . A preliminary report of these fi ndings has appeared [37] , including brief observations about DPT's activity at another 7TMD/ GPC serotonin receptor [27,42] , the rat 5-HT2aR.…”

Nuclear factor‐κB as a molecular target for migraine therapy

“…Although its actions are not well understood, parthenolide exhibits low affinity to 5-HT 2A receptor binding activity and blocks serotonin release from platelets, both of uncertain relevance to migraine headache. 39,40 In addition, it reportedly inhibits the activity of IKK␤ or the p65 binding activity of NF-B. Hehner and colleagues showed that parthenolide inhibits activation of the IKK␤ induced by TNF.…”