Fig. 1: Pharmacological and pharmacokinetic characterization of triazole 187 compared to U50,488 and triazole 1.1.
A Structures of triazole 1.1 and triazole 187. B 35S-GTPyS binding; C βarrestin2 recruitment; D inhibition of forskolin-stimulated cAMP accumulation; and E ERK1/2 phosphorylation are presented as % maximal U69,593 response. Data are presented as mean ± SEM; potencies with 95% CI and n are detailed in F. F Pharmacological parameters (mean with 95% CI) and bias factors are presented where bias factors were calculated using U69,593 as the reference agonist to define unity. ND: not determined, *p < 0.05, ****p < 0.0001; Extra sum of squares F test (p = 0.05) comparing curves of replicates to U69,593; ^p < 0.05; ^^^^p < 0.0001 Extra sum of squares F test (p = 0.05) comparing curves of replicates to triazole 1.1. G Bias factors are plotted on a logarithmic scale (base 10) (10^ΔΔLogR) in the web plot; as presented, a value of >10 indicates a preference for the numerator. H Pharmacokinetic properties of triazole 187 compared to triazole 1.1 measured in C57BL6/J male mice: shown are plasma (left) and brain (right) levels after intraperitoneal injection (i.p.) over time at the doses indicated presented as mean ± SD (n = 3 brains; n = 3 plasma except n = 6 triazole 1.1 s.c. at 60 min and n = 6 for triazole 187 i.p. at 30 min).
