. 2021 Aug 6;9(4):e00799. doi: 10.1002/prp2.799

TABLE 3.

Log K_D values from ³H‐prazosin whole‐cell binding (from Table 1), log EC₅₀ values, and % ionomycin maximal responses obtained from intracellular calcium mobilization and intrinsic efficacy ratios (K_D /EC_{50 calcium}) obtained from CHO‐α1B cells. The log EC₅₀ values obtained from ERK1/2‐phosphorylation (and % PDBu responses), and those obtained from cAMP accumulation (and % forskolin maximum response), and cAMP accumulation in the presence of forskolin (with fold increase of that response) are also given

CHO‐α1B	³H‐prazosin binding	Intracellular calcium release			Log efficacy ratio	ERK1/2‐phosphorylation			cAMP accumulation			cAMP accumulation (in presence of forskolin)
CHO‐α1B	³H‐prazosin binding	Log EC₅₀	% ionomycin	n	K_D /EC₅₀	Log EC₅₀	% PDBu	n	Log EC₅₀	% forskolin	n	Log EC₅₀	Fold increase	n
Adrenaline	−3.94	−9.41 ± 0.13	59.8 ± 3.3	9	5.47	−7.60 ± 0.15 ^a	76.6 ± 9.0	6	−5.43 ± 0.02	172.1 ± 11.3	5	−5.60 ± 0.11	3.14 ± 0.09	5
Noradrenaline	−3.79	−9.23 ± 0.10	62.5 ± 1.2	8	5.44	−7.62 ± 0.04 ^a	75.0 ± 8.8	6	−5.46 ±−0.02	155.5 ± 7.4	5	−5.93 ± 0.10	2.99 ± 0.06	5
R‐phenylephrine	−3.87	−9.04 ± 0.10	67.0 ± 3.3	6	5.17	−7.84 ± 0.10	77.0 ± 4.8	8	−6.11 ± 0.07	86.2 ± 5.3	5	−7.40 ± 0.11	2.43 ± 0.08	5
α‐Methylnorepin ephrine	IC₅₀ > −3	−8.10 ± 0.11	69.1 ± 2.6	8	>5.10	−6.75 ± 0.13	90.6 ± 4.4	9	100 µM	129.7 ± 20.5	5	−5.56 ± 0.05	3.09 ± 0.21	5
Etilefrine	IC₅₀ > −3	−7.86 ± 0.14	61.1 ± 2.1	9	>4.86	−6.52 ± 0.11	78.8 ± 6.1	7	100 µM	73.4 ± 7.1	5	−6.18 ± 0.13	2.47 ± 0.09	5
Dopamine	−2.89	−7.15 ± 0.08	62.5 ± 2.9	6	4.26	−5.83 ± 0.12	85.8 ± 6.0	7	−4.59 ± 0.08	53.0 ± 7.5	5	−5.26 ± 0.02	3.06 ± 0.14	5
Synephrine	IC₅₀ > −3	−7.09 ± 0.12	57.5 ± 1.9	5	>4.09	−5.78 ± 0.08	95.1 ± 8.7	6	100 µM	23.2 ± 2.5	5	−5.94 ± 0.09	2.38 ± 0.17	5
Metaraminol	IC₅₀ > −3	−6.95 ± 0.11	60.1 ± 3.1	7	>3.95	−5.84 ± 0.15	92.2 ± 3.9	6	100 µM	42.0 ± 5.1	5	−5.83 ± 0.08	2.58 ± 0.07	5
ST‐91	−4.39	−8.13 ± 0.17	62.0 ± 2.1	11	3.74	−7.33 ± 0.12	83.6 ± 8.9	6	−6.52 ± 0.04	30.4 ± 3.5	5	−7.23 ± 0.07	2.34 ± 0.09	5
Guanfacine	−3.87	−7.57 ± 0.07	59.0 ± 2.4	7	3.70	−6.71 ± 0.14	97.4 ± 2.7	7	−5.79 ± 0.04	39.0 ± 5.8	5	−6.49 ± 0.14	2.67 ± 0.18	5
Methoxamine	IC₅₀ > −3	−6.64 ± 0.08	59.1 ± 3.2	7	>3.64	−5.55 ± 0.09	83.8 ± 5.7	7	100 µM	24.2 ± 4.6	5	−5.16 ± 0.12	2.42 ± 0.05	5
Isoprenaline	−2.80	−6.16 ± 0.13	53.9 ± 3.3	9	3.36	−5.36 ± 0.10	77.8 ± 8.5	7	ND			ND
Moxonidine	−3.47	−6.49 ± 0.05	57.9 ± 2.1	7	3.02	−6.04 ± 0.15	102.0 ± 6.5	6	ND			ND
Cirazoline	−5.10	−8.05 ± 0.10	53.3 ± 1.5	6	2.95	−6.92 ± 0.11	82.5 ± 8.6	8	−6.92 ± 0.15	11.4 ± 2.4	5	−7.40 ± 0.10	2.09 ± 0.13	5
Octopamine	IC₅₀ > −3	−5.91 ± 0.13	54.9 ± 2.9	6	>2.91	−5.11 ± 0.19	76.1 ± 6.8	6	ND			ND
Tizanidine	−4.35	−7.05 ± 0.08	48.8 ± 1.8	12	2.70	−6.54 ± 0.15	57.7 ± 5.3	6	−6.15 ± 0.17	10.7 ± 1.5	5	−6.74 ± 0.11	2.01 ± 0.11	5
Clonidine	−5.13	−7.77 ± 0.14	45.4 ± 2.1	8	2.64	−7.05 ± 0.12	60.6 ± 7.6	6	−6.60 ± 0.20	7.5 ± 0.8	4	−7.35 ± 0.10	1.67 ± 0.16	5
Para‐amino‐clonidine	−5.17	−7.79 ± 0.05	33.7 ± 2.4	8	2.62	−7.25 ± 0.08	32.8 ± 6.9	6	−7.48 ± 0.43	2.5 ± 0.6	5	−7.31 ± 0.11	1.46 ± 0.04	5
A61603	IC₅₀ > −4	−6.52 ± 0.08	35.7 ± 3.7	10	>2.52	−5.75 ± 0.11	54.5 ± 7.9	9	−5.63 ± 0.18	5.3 ± 0.5	5	−6.16 ± 0.09	1.79 ± 0.05	5
Fenoterol	−3.91	−6.27 ± 0.10	38.0 ± 3.2	6	2.36	−5.56 ± 0.20	33.8 ± 7.3	7	ND			ND
Brimonidine	−4.68	−7.01 ± 0.11	35.8 ± 2.4	8	2.33	−6.14 ± 0.08	41.2 ± 6.2	6	−6.89 ± 0.12	4.5 ± 1.6	5	−6.98 ± 0.09	1.58 ± 0.07	5
Naphazoline	−5.74	−8.03 ± 0.10	38.9 ± 2.9	8	2.29	−6.82 ± 0.09	71.1 ± 7.2	9	−7.89 ± 0.17	3.9 ± 0.7	4	−8.26 ± 0.11	1.65 ± 0.07	5
Dexmedetonidine	−5.04	−7.33 ± 0.06	43.6 ± 2.1	8	2.29	−6.88 ± 0.14	55.4 ± 7.4	6	−7.05 ± 0.15	3.7 ± 0.6	5	−7.48 ± 0.10	1.60 ± 0.07	5
UK14304	−4.89	−7.15 ± 0.05	27.5 ± 1.8	5	2.26	−6.50 ± 0.15	33.8 ± 5.0	6	−7.02 ± 0.18	2.7 ± 0.1	5	−7.01 ± 0.15	1.50 ± 0.05	5
Oxymethazoline	−5.17	−7.42 ± 0.11	27.5 ± 3.6	7	2.25	−7.33 ± 0.11 ^b	67.9 ± 11.3	6	−6.66 ± 0.08	1.4 ± 0.4	4	−6.53 ± 0.12	1.20 ± 0.04	5
Salbutamol	IC₅₀ > −3	−5.14 ± 0.11	58.4 ± 3.0	5	>2.14	100 µM	7.1 ± 3.5	5	ND			ND
Xylazine	−3.22	−5.33 ± 0.14	30.4 ± 3.9	8	2.11	−5.17 ± 0.14	26.4 ± 5.8	6	ND			ND
Medetomidine	−4.84	−6.93 ± 0.13	43.0 ± 3.4	8	2.09	−6.86 ± 0.06	55.2 ± 5.3	6	−6.94 ± 0.19	4.6 ± 0.9	5	−7.03 ± 0.06	1.52 ± 0.04	5
Formoterol	−4.47	−6.56 ± 0.14	18.6 ± 1.6	9	2.09	No response		6	No response		5	−6.55 ± 0.13	1.27 ± 0.02	5
Idazoxan	−4.88	−6.95 ± 0.12	25.7 ± 3.0	10	2.07	−6.18 ± 0.11	31.3 ± 2.2	5	−6.76 ± 0.23	2.4 ± 0.3	4	−6.84 ± 0.06	1.50 ± 0.04	5
Allyphenyline	−5.11	−7.10 ± 0.07	39.9 ± 1.9	5	1.99	−6.55 ± 0.12	65.3 ± 3.0	6	−6.76 ± 0.12	5.5 ± 0.9	5	−7.29 ± 0.10	1.87 ± 0.07	5
Detomidine	−5.65	−7.49 ± 0.11	33.8 ± 1.7	7	1.84	−7.17 ± 0.09	31.5 ± 5.4	6	−7.90 ± 0.09	2.8 ± 0.6	5	−7.89 ± 0.15	1.57 ± 0.07	5
Buspirone	−4.65	−6.42 ± 0.09	47.8 ± 3.2	5	1.77	−6.05 ± 0.18	47.2 ± 8.6	6	ND			ND
Guanabenz	−5.45	−7.03 ± 0.12	33.7 ± 4.7	8	1.58	−5.86 ± 0.18	44.9 ± 7.9	6	−7.12 ± 0.13	2.3 ± 0.8	5	−7.09 ± 0.18	1.49 ± 0.05	5
Lisuride	−6.07	−7.23 ± 0.22	15.8 ± 2.2	12	1.16	−6.51 ± 0.16 ^b	73.1 ± 8.0	5	No response		5	No response		5
Rilmenidine	IC₅₀ > −3	100 µM	20.0 ± 3.9	5		No response		5	ND			ND
Epdedrine	IC₅₀ > −3	100 µM	18.5 ± 2.9	9		−4.67 ± 0.17	19.1 ± 4.0	7	ND			ND
Atipamezole	−4.68	100 µM	18.1 ± 4.8	5		No response		5	ND			ND
Midodrine	No binding	100 µM	16.9 ± 2.0	10		100 μM	20.4 ± 8.0	6	ND			ND
BHT933	No binding	100 µM	16.6 ± 2.1	6		ND			ND			ND
BHT920	−3.73	100 µM	16.3 ± 4.5	6		−5.31 ± 0.04	12.2 ± 3.6	6	ND			ND
Salmeterol	−5.13	10 µM	15.2 ± 4.0	5		ND			ND			ND
BRL44408	−4.68	100 µM	13.7 ± 6.5	5		100 μM	47.0 ± 7.0	6	ND			ND
Xylometazoline	−5.16	100 μM	13.6 ± 3.3	8		−6.71 ± 0.16 ^b	66.2 ± 6.0	6	No response		5	−8.04 ± 0.18 ^c	13.5 ± 1.8%a	5
Chloroethylclonidine	−5.35	100 µM	10.2 ± 2.0	5		No response		6	ND			ND
RWJ52353	IC₅₀>−3	10 μM	8.1 ± 3.1	5		ND			ND			ND
BMY7378	−6.23	100 µM	8.0 ± 2.1	9		No response		6	ND			ND
Sunepitrion	−4.65	100 μM	8.2 ± 1.3	9		?−6.36 ± 0.29	7.8 ± 2.8	7	ND			ND
Dihydroergotamine	−6.92	10 µM	6.4 ± 2.1	5		−7.85 ± 0.13 ^b	50.1 ± 4.8	6	ND			ND
PF3774076	−4.74	10 µM	5.2 ± 1.7	5		No response		6	ND			ND
ARC239	−8.15	100 µM	4.8 ± 1.7	5		No response		5	ND			ND
3‐MPPI	−8.59	100 µM	4.6 ± 1.9	7		No response		5	ND			ND
2‐MPMDQ	−7.37	100 µM	3.1 ± 1.5	5		No response		5	ND			ND
Dobutamine	−5.44	100 µM	3.0 ± 1.1	8		100 μM	56.3 ± 11.3	6	No response		5	−5.70 ± 0.07	1.24 ± 0.04	5
Tetrohydrozoline	−5.22	100 µM	2.9 ± 1.4	5		No response		6	ND			ND
Labetolol	−5.91	100 µM	2.5 ± 1.2	7		−5.42 ± 0.14 ^b	22.9 ± 6.3	6	No response		5	No response		5
CGP 12177	IC₅₀ > −4	No response		5		−5.98 ± 0.12 ^b	38.1 ± 3.8	6	ND			ND
Eforaxan	−4.27	No response		5		100 μM	11.9 ± 2.4	7	ND			ND
T‐CG 1000	−5.18	No response		6		ND			ND			ND
2‐PMDQ	−6.95	No response		5		No response		7	ND			ND
Amitraz	IC₅₀ > −4	No response		5		ND			ND			ND
Methyldopa	No binding	No response		5		ND			ND			ND

Values represent mean ± SEM of n separate experiments. The ligands are arranged in order of intrinsic efficacy ratio as determined from the calcium response (EC₅₀) and binding (K_D ).

Abbreviation: ND, not determined.

^{^a}

These compounds had a bi‐phasic response. Log EC₅₀ and % PDBu given for initial stimulatory part of response.

^{^b}

These compounds stimulate ERK1/2‐phosphorylation in parent CHO cells, see Supplementary data Table S1, Figure S1.

^{^c}

Xylometazoline caused a decrease in forskolin‐stimulated cAMP accumulation. The data given are log IC₅₀ and % inhibition of forskolin‐stimulated cAMP.