Table 1.
Model | Parameter | Phenylephrine | Oxymetazoline | Naphazoline | Clonidine | Tolazoline |
---|---|---|---|---|---|---|
(A) Experimental data from Ruffolo et al. (1979) | ||||||
E max | 1.00 | 0.73 | 0.48 | 0.33 | 0.10 | |
log ED50 | −7.55 | −6.77 | −8.20 | −7.60 | −6.64 | |
log K d 1 | −6.46 | −6.36 | −8.23 | −7.66 | −6.69 | |
(B) Standard E max (Prism: log[agonist] vs. response ‐ variable slope [four parameters], eq. 9; Hill slope = 1, Bottom = 0) | ||||||
Top | 99.6 ± 1.26 | 72.9 ± 1.04 | 48.0 ± 0.56 | 33.2 ± 0.70 | 10.0 ± 1.08 | |
LogEC50 | −7.55 ± 0.035 | −6.77 ± 0.029 | −8.20 ± 0.027 | −7.60 ± 0.047 | −6.64 ± 0.174 | |
r 2 | 0.9958 | 0.9978 | 0.9972 | 0.9937 | 0.9491 | |
SSE | 56.25 | 10.50 | 4.26 | 7.52 | 2.95 | |
(C) Present (Prism implementation of present model, eq. 31 with no amplification γ = 1 [i.e., eq. 26] [n = 1]) | ||||||
ε | 0.996 ± 0.0126 | 0.729 ± 0.0104 | 0.480 ± 0.0056 | 0.332 ± 0.0070 | 0.100 ± 0.0108 | |
γ | 1 | 1 | 1 | 1 | 1 | |
log K d | −7.55 ± 0.035 | −6.77 ± 0.029 | −8.20 ± 0.027 | −7.60 ± 0.047 | −6.64 ± 0.174 | |
r 2 | 0.9958 | 0.9978 | 0.9972 | 0.9937 | 0.9491 | |
SSE | 56.25 | 10.50 | 4.26 | 7.52 | 2.95 | |
(D) Operational model [Prism implementation for partial agonist, eq. 19; n (Hill) = 1, Basal = 0] | ||||||
Effectmax | 99.58 ± 0.826 | 99.58 ± 0.826 | 99.58 ± 0.826 | 99.58 ± 0.826 | 99.58 ± 0.826 | |
logK A | (n.u.)b/~ −1.527 ± 6082 | −6.20 ± 0.051 | −7.91 ± 0.056 | −7.42 ± 0.078 | −6.59 ± 0.312 | |
τ | (n.u.)b/~106.0 b ± too wide | 2.731 ± 0.196 | 0.931 ± 0.042 | 0.499 ± 0.025 | 0.112 ± 0.024 | |
LogEC50 | −7.55 ± 0.023/(n.u.) | (not used) | (not used) | (not used) | (not used) | |
r 2 | 0.9958 | 0.9978 | 0.9972 | 0.9937 | 0.9491 | |
SSE | 56.25 | 10.50 | 4.26 | 7.52 | 2.95 | |
(E) Present (Prism implementation of present model, eq. 31; K d from experimental [n = 1]) | ||||||
ε | 1 | 0.1739 ± 0.0274 | 0.0637 ± 0.0106 | 0.0369 ± 0.0064 | 0.0088 ± 0.0022 | |
γ | 11.88 ± 2.02 | 11.88 ± 2.02 | 11.88 ± 2.02 | 11.88 ± 2.02 | 11.88 ± 2.02 | |
log K d (from exp.)a | −6.46 | −6.36 | −8.23 | −7.66 | −6.69 | |
↓c | ||||||
E max | 1.000 | 0.714 | 0.447 | 0.313 | 0.096 | |
log EC50(K obs) | −7.53 | −6.82 | −8.46 | −7.81 | −6.73 | |
r 2 | 0.9957 | 0.9964 | 0.9508 | 0.9736 | 0.9430 | |
SSE | 57.22 | 17.21 | 76.18 | 31.71 | 3.30 |
All fitting were done with models implemented in GraphPad Prism, and in addition to the calculated parameters (shown with their calculated standard errors), descriptors of the quality of fit (correlation coefficient, r 2, and sum of squared errors, SSE) are also included.
Experimental data, average of log K A (Table 3) and log K B (Table 4) from Ruffolo et al. (1979).
The operational model as implemented in GraphPad Prism, does not fit K A and τ for a full agonist (not used) as well‐defined values cannot be obtained. A set of values were calculated here for illustration by re‐using the data of the full agonist (phenylephrine) as another partial agonist.
Derived values for the present model (using eq. 33).