Table 1.
Affinity (95% confidence interval) values of subtype-selective muscarinic receptor antagonists for inhibition of carbachol-induced bladder contraction and their reported affinity for the M2 and M3 receptor subtypes
| Group | Methoctramine | 4-DAMP | p-F-HHSiD | Darifenacin |
|---|---|---|---|---|
| Sham operated | 6.0–6.4 | 8.9–9.1 | 7.6–7.8 | 8.3–8.7 |
| DIV | 6.0–6.4 | 7.2–7.6 | 8.7–9.1 | |
| DIV-DEN | 6.1–6.5 | 7.2–7.6 | 8.6–9.2 | |
| DEN | 6.3–6.7 | 8.3–8.7 | 6.8–7.2 | 7.5–8.5 |
| BOO | 5.9–6.5 | 6.5–7.1 | 7.8–8.4 | |
| MPG-DEC | 4.4–5.6 | 6.5–7.1 | 7.5–7.9 | |
| M2* | 7.8–8.3 | 8.0–8.4 | 6.0–6.9 | 7.0–7.4 |
| M3* | 6.3–6.9 | 8.9–9.3 | 7.8–7.9 | 8.4–8.9 |
Values are 95% confidence intervals; 6–8 muscle strips were used per antagonist concentration. Nonoverlapping confidence intervals denote a statistically significant difference (P < 0.05). The affinities for 4-DAMP, methoctramine, and p-F-HHSiD were determined by Schild analysis. Concentrations of 0.3 and 3.0 µM methoctramine and p-F-HHSiD were used, while 3.0, 10.0, and 30.0 nM 4-DAMP were used. The estimated pKb for darifenacin was determined based on a single 30 nM darifenacin concentration.
Adapted from Caulfield (7) and Caulfield and Birdsall (8), which include both functional and ligand binding studies. DIV, urinary diversion; DIV-DEN, major pelvic ganglion (MPG) electrocautery (MPGE) together with urinary diversion; DEN, bilateral MPGE; BOO, bladder outlet obstruction; MPG-DEC, MPG decentralization; 4-DAMP, 4-diphenacetoxy-N-methylpiperidine methiodide; p-F-HHSiD, para-fluoro-hexahydrosila-diphenidol.