Estimates of [3H]NMS log affinity (logm −1) of brucine analogues at [3H]NMS-occupied muscarinic receptors
| Analogue | Receptor subtype | ||||
|---|---|---|---|---|---|
| m1 | m2 | m3 | m4 | m5 | |
| Brucine | 4.50 ± 0.06 (5) | 4.62 ± 0.05 (3) | 3.21 ± 0.15 (5) | 4.52 ± 0.06 (5) | 2.94 ± 0.08 (2) |
| CMB | 4.09 ± 0.05 (5) | 4.63 ± 0.03 (4) | 3.27 ± 0.12 (6) | 4.37 ± 0.08 (6) | 3.20 ± 0.02 (2) |
| BNO | 3.23 ± 0.06 (6) | 3.49 ± 0.03 (4) | 2.52 ± 0.04 (6) | 3.55 ± 0.05 (6) | 2.33 ± 0.03 (2) |
| N-Benzyl brucine | 4.37 ± 0.05 (3) | 4.84 ± 0.13 (3) | 3.77 ± 0.05 (3) | 4.53 ± 0.08 (3) | 3.72 ± 0.01 (2) |
| Strychnine2-a | 4.9 | 5.2 | 4.2 | 5.0 | 3.62 ± 0.05 (2) |
Values are shown as mean ± standard error (n) and were derived from the single-time point off-rate assay data as described in the text.
The dissociation times were 20, 4, 25, 25, and 44 min for m1—m5 receptors, respectively.
The [3H]NMS dissociation rate constants (min−1) measured at these dissociation times were 0.075 ± 0.006, 0.361 ± 0.018, 0.064 ± 0.003, 0.066 ± 0.003, and 0.033 ± 0.001 for m1—m5 receptors, respectively, withn = 13 for m1—m4 receptors and n = 7 for m5 receptors, corresponding to dissociation half-lives of 9.2, 1.9, 10.8, 10.5, and 21 min, respectively.
↵2-a Values at m1—m4 receptors are from Lazareno and Birdsall (1995).