Table 2. Potency and efficacy (as % of acetylcholine response) of clozapine and its metabolites at recombinant human muscarinic receptors.
| Compound | hM1 | hM2 | hM3 | hM4 |
|---|---|---|---|---|
| Acetylcholine | 21 ± 6 (100) | 1,003 ± 235 (100) | 5.2 ± 1.8 (100) | 837 ± 192 (100) |
| Clozapine | 293 ± 87 (11 ± 1) | 0% at 100 μM | 5 ± 3% at 100 μM | 0% at 100 μM |
| N-desmethylclozapine | 115 ± 28 (50 ± 5) | 857 ± 598 (38 ± 9) | 2 ± 1.6 μM (15 ± 4) | 0% at 100 μM |
| Clozapine-N-oxide | 8 ± 1.5 μM (23 ± 4) | 0% at 100 μM | 0% at 100 μM | 0% at 100 μM |
EC50 values are mean ± SEM of 3-10 determinations and are expressed in nM unless otherwise specified. Data for hM1 and hM3 and for hM2 and hM4 are from FLIPR experiments and GTPγS assay, respectively. Numbers in parentheses are percentages of acetylcholine response.