Summary of in vitro pharmacology results for (+)-6-OH-7-Cl-PAT, (−)-6-OH-7-Cl-PAT, (+)-6-OMe-7-Cl-PAT, and (−)-6-OMe-7-Cl-PAT
Ki and receptor-mediated PLC activity values (mean ± S.E.M.) obtained from at least three independent experiments. [3H]Ketanserin and [3H]mesulergine were used to label 5-HT2A and 5-HT2C receptors, respectively. Emax was defined as the percent of maximal response to 5-HT. Ki values and functional outcomes of each compound at h5-HT2B receptors were also obtained (see Results). Note the distinct difference in pharmacology between the (+)- and (−)-enantiomers of 6-OH-7-Cl-PAT at h5-HT2A compared with m5-HT2A receptors. (+)-6-OH-7-Cl-PAT showed partial agonist activity at h5-HT2A receptors but was inactive at all other WT 5-HT2 receptors tested.
| Ligand | h5-HT2A | m5-HT2A | h5-HT2C | m5-HT2C | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ki | Function | EC50 | Emax | Ki | Function | EC50 | Emax | Ki | Function | EC50 | Emax | Ki | Function | EC50 | Emax | |
| nM | nM | % | nM | nM | % | nM | nM | % | nM | nM | % | |||||
| 5-HT | 128a | Full agonist | 127 (24) | 100 | 138a | Full agonist | 56 (7.5) | 100 | 15a | Full agonist, | 11 (2.7) | 100 | 50a | Full agonist | 18 (2.8) | 100 |
| (+)-6-OH-7-Cl-PAT | 80 (4.4) | Partial agonist | 125 (32) | 36 (10) | 3005 (321)*** | No activation | 1079 (42.9) | No activation | 3651 (481)** | No activation | ||||||
| (−)-6-OH-7-Cl-PAT | 69 (4.9) | No activation | 58 (6.8) | No activation | 21 (2.4) | No activation | 51 (9.5)* | No activation | ||||||||
| (+)-6-OMe-7-Cl-PAT | 176 (18) | No activation | 173 (29) | No activation | 47 (5.3) | No activation | 243 (22)** | Partial agonist | 1359 (178) | 59 (4.0) | ||||||
| (−)-6-OMe-7-Cl-PAT | 134 (18) | No activation | 119 (12) | No activation | 30 (3.3) | Partial agonist | 127 (8.6) | 71 (8.2) | 98 (15)* | Partial agonist | 29 (5.4) | 80 (5.4) | ||||
a From Canal et al., 2013.
* P < 0.05; **P < 0.01; ***P < 0.001 vs. human ortholog.