Errata

In Journal of Receptors and Signal Transduction, 24(3): 207–239, 2004 for the article “Dopamine Receptor Microdomains Involved in Molecular Recognition and the Regulation of Drug Affinity and Function,” incorrect data was included. The affected items appear in corrected form below.

Page 209, Section II, Paragraph 2, Sentence 1, should appear as: Substitution of the primary amine of dopamine with a quaternary trimethylamine (DA-N(Me)₃) results in a large reduction in the binding to the agonist high-affinity and low-affinity state of the receptor (263-fold and 199-fold, respectively, Table 1) (9).

Table 1 Affinity and potency values for dopamine, and its uncharged and permanently positively-charged analogs and bioisosters

		Affinity, nM
Name, abbreviation	Chemical structure	Ki	Klow	Khigh	Potency (EC50), nM	Ref.
Protonatable Dopamine, DA			354 (1)	10 (1)	1930 (1)	1
N-Dimethyldopamine, DA-N(Me)2			724 (2.1)	25 (2.5)	60 (−32)	1
			720	25	nt	2
			(1.8)	(2.5)
Permanently-Charged Dopamine derivatives
N-Trimethylammonium DA-N+(Me)3			70600 (199)	2630 (263)	7490 (3.9)	1
N-Dimethylselenonium DA-Se+N(Me)2			22900 (64.7)	541 (54)	8990 (4.7)	1
N-Dimethylsulfonium DA-S+N(Me)2			76900 (217)	1280 (128)	22,700 (12)	1
Premanently-Uncharged Dopamine derivatives
Monomethylsulfide DA-S(Me)		16,100			Inactive	2
Monomethylselenide DA-Se(Me)		3800			nt	2
Monomethylsulfoxide DA-SO(Me)		32,700			Inactive	2

References Numbering:

1. Wallace et al., 1987.

2. Wallace et al., 1988.

The affinity values are listed first and the values in parentheses underneath refer to the fold-change difference relative to that reported for dopamine. Negative values indicate an higher affinity for the derivative than for dopamine. K_high and K_low values are listed for binding that is best-fit as two-site.

*Only K_i values and no fold-changes are listed for binding that is best-fit as one-site. The abbreviation “nt” means not tested.

Page 212, Paragraph 1, Sentence 3, should appear as: Although the dopamine-like dimethylselenonium and dimethylsulfonium derivatives had drastically reduced affinity for the high-affinity state, their potency was only moderately decreased (4.7-fold and 12-fold, respectively, Table 1) (9). Page 212, Paragraph 2, Sentence 2, should appear as: For instance, substitution of the dimethylamino group of the phenothiozine chlorpromazine for permanently charged quaternary trimethylamino or dimethylsulfide groups drastically reduces binding affinity (1792-fold and 233-fold respectively) and moderately reduces the potency of functional antagonism (11-fold and 19-fold, respectively; Table 2) (12).

Table 2 Affinity and potency values for the sodium-sensitive substituted benzamide antagonists metclopramide and sulpiride, and the sodium-insensitive phenothiozine antagonist chlorpromazine, and their differentially-charged analogs and bioisosters

		Binding affinity, nM
Name, abbreviation	Chemical structure	Ki	Klow	Khigh	Functional antagonism equilibrium dissociation constant (Kb), μ M	Ref.
Protonatable Metoclopramide, met-N(et)2			36,040 (1)	600 (1)	0.09 (1)	1,2
met-N(me)2			75,340 (2.1)	1190 (2)	0.18 (2)	1,2
Permanently-Charged met-N+(me)3			> 637,000 (> 18)	86,740 (145)	5.1 (57)	1,2
met-N+(me)2(et)			> 874,200 (> 24)	52,350 (87)	3.9 (43)	1,2
met-N+(me)(et)2			> 516,800 (> 14)	79,710 (133)	Inactive	1,2
met-S+(me)2			809,290 (23)	52,350 (87)	2.1 (23)	1,2
Protonatable Sulpiride N-et			nt	nt	320 (1)	3
Permanently-Charged Sulpiride N+(et)(me)			nt	nt	1090 (3.4)	3
Sulpiride N+(et)2			nt	nt	1220 (3.8)	3
Sulpiride S+(et)			nt	nt	5000 (16)	3
Permanently-Uncharged Sulpiride S			nt	nt	Inactive	3
Protonatable Chlorpromazine, CPZ-N(Me)2		1.2 (1)			0.072 (1)	4
Permanently-Charged CPZ-N+(Me)3		2150 (1792)			0.77 (11)	4
CPZ-S+(Me)2		280 (233)			1.35 (19)	4

References Numbering:

1. Harrold et al., 1993.

2. Farooqui et al., 1994.

3. Harrold et al., 1989.

4. Harrold et al., 1987.

The affinity values are listed first. The values in parentheses underneath refer to the fold-change difference relative to the native metoclopramide, sulpiride, or chlorpromazine. In constrast to agonists, the affinity of many substituted benzamide antagonists are increased by sodium, thus K_low values were determined by measuring the affinity in the absence of 125 mM sodium. The functional antagonism equilibrium dissociation constant (Kb) is defined by the equation Kb=[B]/ (DR-1) where B is the concentration of antagonist used, and DR (dose-ratio) is the concentration of the agonist required to produce a half-maximal effect in the presence and absence of antagonist. The abbreviation “nt” means not tested.

Table 4 Affinity values for the binding agonists and antagonists to cloned wild type D3 dopamine receptors and the corresponding S5.42A, S5.43A, and S5.46A mutants

		Binding affinity (Ki or Kd, nM)
Name	Chemical structure	D3-WT	D3-S5.42A	D3-S5.43A	D3-S5.46A
Dopamine		36 (1)	2,234 (62)	75 (2.1)	31 (−1.2)
7OH-DPAT		17 (1)	53 (3.1)	15 (1.1)	9.5 (−1.8)
Quinpirole		70 (1)	81 (1.2)	74 (1.1)	57 (−1.2)
Spiperone		0.18 (1)	0.13 (−1.4)	0.065 (−2.8)	0.11 (−1.6)

Data taken from Sartania and Strange, 1999. For dopamine, 7OH-DPAT, and quinpirole, K_i was measured under low affinity conditions (i.e., done in the presence of 100 μM GTP). The values in parentheses refer to the fold-changes relative to the wild type receptor. Negative values indicate a higher affinity for the mutant than the wild type receptor.

Table 8 Affinity values for the binding of antagonists to cloned wild type D2 dopamine receptor and the corresponding S5.42C, S5.43C, and S5.46C mutants

Name	Chemical structure	D2-WT (C3.36S)	D2- S5.42C	D2- D2-S5.43C	D2- S5.46C
Methylspiperone		0.088	0.033 (−2.7)	0.085 (1)	0.035 (−2.5)
(−)-Sulpiride		8	0.7 (−11)	17 (2.1)	110 (14)

Data taken from Javitch et al. (1995). Note that what is referred to as the wild type D2 dopamine receptor background actually has a C3.36S mutation. Accordingly, all the TM5 serine to cysteine mutants additionally have the C3.36S mutation. The value in parentheses refer to the fold-changes relative to the wild type receptor. Negative values indicate a higher affinity for the mutant than the wild type receptor.

Table 9 Affinity of various non-selective or moderately-selective mono- or disubstituted aromatic piperidinyl/piperizinyl antagonists

		Binding affinity (Ki, nM)
Drug	Structure	D2-WT	D4-WT	D4-F2.61V	D4-LM 3.28-3.29 FV
Clozapine		10 (2.7)	3.9 (1)	9.7 (2.5)	3.8 (1)
Olanzapine		1.2 (−3.5)	4.2 (1)	8.2 (1.9)	8.2 (1.9)
Quetiapine		24 (−14)	341 (1)	493 (1.4)	222 (−1.5)
Ziprasidone		0.28 (−27)	7.5 (1)	5.6 (−1.4)	15 (1.9)
Risperidone		0.40 (−9.5)	3.8 (1)	2.4 (−1.6)	39 (10)

Unpublished data from J.A. Schetz. The values in parentheses refer to fold-changes relative to the wild type D4 receptor. Negative values indicate a higher affinity than for the wild type D4 receptor.

Page 226, Paragraph 1, Sentence 6, should appear as: The D1-S5.43A mutant has reduced affinity for the catechol-containing agonists SKF38393 and SKF82958 (4.5-fold and 13-fold, respectively) and an even greater reduction in affinity for the structural analogue antagonist SCH23390 (72-fold; Table 5) (24).

Page 229, Paragraph 2, Sentence 8, should appear as: The H6.55 must be acting as an H-bond donor in this interaction, because neither cysteine nor leucine can donate H-bonds and sultopride can only act as an H-bond acceptor.

Page 229, Paragraph 2, Sentence 10 should appear as: The D2-F6.52C mutant had only slightly reduced affinity (3- to 4-fold) for [³H]methylspiperone and [³H]sulpiride (30), but the affinity for [³H]methylspiperone, [³H]raclopride, [³H]N-0437 was abolished in a D2-F6.52A mutant (36).

Page 230, Section VI, Paragraph 1, Sentence 4 should appear as: In the case of the β 2-adrenergic receptor, the charge-neutralizing mutations, D3.49N, E6.30A, and E6.30Q, increase both basal and pindolol-stimulated cAMP accumulation relative to the wild-type receptor (38).

Page 231, Section VIII, Paragraph 1, Sentence 4 should appear as: Furthermore, the affinity for another benzazapine antipsychotic olanzapine is also decreased about 2-fold, even though olanzapine has higher affinity for D2 over D4 receptors (3.5-fold) whereas the more D2-selective (14-fold) benzazapine quetiapine is insensitive to this same D4-F2.61V mutation (Table 9) (42).

Figure 1. Structures of some clinically-relevant dopamine agonists and antagonists. Antagonists are grouped according to structural class.