Figure 6. Antimuscarinic compounds favoring M3 over M2 receptors phenocopy tolterodine treatment in zebrafish embryos.
(A) Live images of 48 hpf embryos after treatment with vehicle (DMSO) or 50 μM solifenacin or zamifenacin. Arrow indicates the edema. Scale bar: 200 μm. (B) Solifenacin treatment caused dose-dependent arrhythmia. n = 3–8 experiments with 85–165 embryos. (C) Zebrafish treated with increasing concentrations of solifenacin developed AV-blocks. n = 3–8 experiments with 85–165 embryos. (D) Solifenacin caused formation of edema with increasing concentrations. n = 3–8 experiments with 85–165 embryos. (E) Zebrafish embryos treated with zamifenacin developed arrhythmia at low micromolar concentrations. At higher concentrations, both chambers became silent. n = 3–6 experiments with 59–144 embryos. (F) Zamifenacin treatment provoked AV-blocks. n = 3–6 experiments with 59–144 embryos. (G) Edema formation occurred in a dose-dependent manner upon zamifenacin treatment. n = 3–6 experiments with 59–103 embryos. Graphs display mean ± SEM.