Table 3.
Potency of MEL-9 and LP-211 as irreversible inhibitors of 5-CT-stimulated cAMP signaling and of whole-cell [3H]-SB-269970 radioligand binding in HEK-hu5-HT7 cells in preincubation/washout experiments
| Potency as irreversible inhibitors of human 5-HT7 receptors in preincubation/washout experiments | ||
|---|---|---|
| 5-CT-stimulated cAMP production | Whole-cell [3H]-SB-269970 radioligand binding | |
| Compound | IC50, irrev (nmol/L) | IC50, irrev (nmol/L) |
| MEL-9 | 41.84 ± 18.03 | 22.42 ± 7.63 |
| LP-211 | 101.65 ± 38.00 | 76.26 ± 25.39 |
IC50, irrev denotes the potency of the compounds as irreversible inhibitors of 5-HT7-mediated cAMP signaling or whole-cell 5-HT7 radioligand binding in assays carried out after preincubation of the cells with the compounds and subsequent compound washout. Data are the mean values ± SEM from three independent experiments performed in triplicate (cAMP assays) or of three independent experiments performed in duplicate (whole-cell radioligand binding). MEL-9, N-benzyl-4-(2-diphenyl)-1-piperazinehexanamide; LP-211, N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide; 5-CT, 5-carboxamidotryptamine; [3H]-SB-269970, (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine; 5-HT7, 5-hydroxytryptamine (serotonin) type 7 receptor.