A<sub>1</sub> receptor | Adenosine receptors | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

A₁ receptor

Target id: 18

Nomenclature: A₁ receptor

Gene and Protein Information
Previous and Unofficial Names
Database Links
Selected 3D Structures
Natural/Endogenous Ligands
Agonists
Antagonists
Allosteric Modulators
Immunopharmacology Comments
Immuno Cell Type Associations
Immuno Process Associations
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
General Comments
References
Contributors
How to cite this page

Gene and Protein Information
class A G protein-coupled receptor
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	7	326	1q32.1	ADORA1	adenosine A1 receptor	86,117,141
Mouse	7	326	1 E4	Adora1	adenosine A1 receptor	95,152
Rat	7	326	13q13	Adora1	adenosine A1 receptor	94

Previous and Unofficial Names
RDC7 \| adenosine receptor A1 \| A1-AR \| A1R

Previous and Unofficial Names

RDC7 | adenosine receptor A1 | A1-AR | A1R

Database Links
Specialist databases
GPCRdb	aa1r_human (Hs), aa1r_mouse (Mm), aa1r_rat (Rn)
Other databases
Alphafold	P30542 (Hs), Q60612 (Mm), P25099 (Rn)
ChEMBL Target	CHEMBL226 (Hs), CHEMBL3688 (Mm), CHEMBL318 (Rn)
DrugBank Target	P30542 (Hs)
Ensembl Gene	ENSG00000163485 (Hs), ENSMUSG00000042429 (Mm), ENSRNOG00000003442 (Rn)
Entrez Gene	134 (Hs), 11539 (Mm), 29290 (Rn)
Human Protein Atlas	ENSG00000163485 (Hs)
KEGG Gene	hsa:134 (Hs), mmu:11539 (Mm), rno:29290 (Rn)
OMIM	102775 (Hs)
Pharos	P30542 (Hs)
RefSeq Nucleotide	NM_000674 (Hs), NM_001008533 (Mm), NM_017155 (Rn)
RefSeq Protein	NP_000665 (Hs), NP_001008533 (Mm), NP_058851 (Rn)
UniProtKB	P30542 (Hs), Q60612 (Mm), P25099 (Rn)
Wikipedia	ADORA1 (Hs)

Selected 3D Structures

Image of receptor 3D structure from RCSB PDB

Description:	Crystal structure of the human adenosine A1 receptor A1AR-bRIL in complex with the covalent antagonist DU172 at 3.2A resolution
PDB Id:	5UEN
Ligand:	DU172
Resolution:	3.2Å
Species:	Human
References:	49

Description:	Crystal structure of stabilized A1 receptor in complex with PSB36
PDB Id:	5N2S
Ligand:	PSB36
Resolution:	3.3Å
Species:	Human
References:	18

Description:	Structure of the adenosine-bound human adenosine A₁ receptor–G_i complex
PDB Id:	6D9H
Ligand:	adenosine
Resolution:	3.6Å
Species:	Human
References:	30

Natural/Endogenous Ligands
adenosine

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Agonists

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Ligand		Sp.	Action	Value	Parameter	Reference
[³H]CCPA		Hs	Full agonist	9.2	pK_d	78,120
⤷	pK_d 9.2 (K_d 6.31x10^-10 M) [78,120]
5-Cl-5-deoxy-(±)-ENBA		Hs	Full agonist	9.3	pK_i	36
⤷	pK_i 9.3 (K_i 5.1x10^-10 M) [36]
N(6)-cyclohexyladenosine		Rn	Agonist	9.1	pK_i	24
⤷	pK_i 9.1 (K_i 8.5x10^-10 M) [24]
(R)-PIA		Rn	Agonist	8.9	pK_i	24
⤷	pK_i 8.9 (K_i 1.2x10^-9 M) [24]
CCPA		Rn	Agonist	8.9	pK_i	85
⤷	pK_i 8.9 (K_i 1.3x10^-9 M) [85]
(R,S)-PHPNECA		Hs	Full agonist	8.6	pK_i	148
⤷	pK_i 8.6 [148]
TCPA		Hs	Agonist	8.6	pK_i	9
⤷	pK_i 8.6 (K_i 2.8x10^-9 M) [9]
GR79236		Rn	Agonist	8.5	pK_i	63
⤷	pK_i 8.5 (K_i 3.1x10^-9 M) [63]
NECA		Rn	Agonist	8.3	pK_i	90
⤷	pK_i 8.3 (K_i 5.1x10^-9 M) [90]
tecadenoson		Pig	Agonist	8.2	pK_i	63,105
⤷	pK_i 8.2 (K_i 6.5x10^-9 M) [63,105]
2-chloroadenosine		Rn	Agonist	8.2	pK_i	24
⤷	pK_i 8.2 (K_i 6.7x10^-9 M) [24]
compound 10 [PMID: 31306001]		Hs	Inverse agonist	8.1	pK_i	8
⤷	pK_i 8.1 (K_i 7.22x10^-9 M) [8] Description: Binding affinity calculated by measuring displacement of specific [³H]DPCPX binding at hA₁ARs expressed in CHO cells.
cyclopentyladenosine		Hs	Full agonist	6.5 – 9.4	pK_i	22,25,41,54,63-64,120
⤷	pK_i 6.5 – 9.4 [22,25,41,54,63-64,120]
CCPA		Hs	Full agonist	7.7 – 8.1	pK_i	63,110
⤷	pK_i 7.7 – 8.1 [63,110]
MRS3558		Mm	Agonist	7.8	pK_i	85
⤷	pK_i 7.8 (K_i 1.58x10^-8 M) [85]
LUF5831		Hs	Partial agonist	7.7	pK_i	54
⤷	pK_i 7.7 [54]
(R)-PIA		Hs	Full agonist	6.4 – 8.7	pK_i	41,64,78,120,140
⤷	pK_i 6.4 – 8.7 [41,64,78,120,140]
Cl-IB-MECA		Mm	Agonist	7.5	pK_i	85
⤷	pK_i 7.5 (K_i 3.5x10^-8 M) [85]
piclidenoson		Hs	Agonist	7.3	pK_i	63
⤷	pK_i 7.3 (K_i 5.1x10^-8 M) [63]
GS9667		Hs	Agonist	7.3	pK_i	34
⤷	pK_i 7.3 (K_i 5.5x10^-8 M) [34]
2-hexynyl-NECA		Hs	Full agonist	7.2	pK_i	148
⤷	pK_i 7.2 [148]
adenosine		Rn	Agonist	7.1	pK_i	155
⤷	pK_i 7.1 (K_i 7.3x10^-8 M) [155]
apadenoson		Hs	Agonist	7.1	pK_i	63
⤷	pK_i 7.1 (K_i 7.7x10^-8 M) [63]
adenosine		Hs	Agonist	~7.0	pK_i	155
⤷	pK_i ~7.0 (K_i ~1x10^-7 M) [155]
MRS3558		Rn	Agonist	7.0	pK_i	85
⤷	pK_i 7.0 (K_i 1.05x10^-7 M) [85]
NECA		Hs	Full agonist	5.3 – 8.2	pK_i	41,64,120,140,155
⤷	pK_i 5.3 – 8.2 [41,64,120,140,155]
Cl-IB-MECA		Hs	Agonist	6.7	pK_i	63
⤷	pK_i 6.7 (K_i 2.2x10^-7 M) [63]
MRS3558		Hs	Agonist	6.6	pK_i	63
⤷	pK_i 6.6 (K_i 2.6x10^-7 M) [63]
Cl-IB-MECA		Rn	Agonist	6.6	pK_i	85
⤷	pK_i 6.6 (K_i 2.8x10^-7 M) [85]
HEMADO		Hs	Agonist	6.5	pK_i	77,148
⤷	pK_i 6.5 (K_i 3.3x10^-7 M) [77,148]
PENECA		Hs	Full agonist	6.2	pK_i	148
⤷	pK_i 6.2 [148]
CGS 21680		Hs	Full agonist	5.8 – 6.4	pK_i	41,63
⤷	pK_i 5.8 – 6.4 [41,63]
CGS 21680		Rn	Agonist	5.7	pK_i	85
⤷	pK_i 5.7 (K_i 1.8x10^-6 M) [85]
2-chloroadenosine		Hs	Full agonist	5.2 – 5.6	pK_i	64,120
⤷	pK_i 5.2 – 5.6 [64,120]
(S)-PIA		Hs	Full agonist	4.6 – 6.0	pK_i	64,140
⤷	pK_i 4.6 – 6.0 [64,140]
CP608,039		Hs	Agonist	5.1	pK_i	63
⤷	pK_i 5.1 (K_i 7.3x10^-6 M) [63]
BAY 60-6583		Hs	Agonist	<5.0	pK_i	81
⤷	pK_i <5.0 (K_i >1x10^-5 M) [81]
regadenoson		Hs	Agonist	<5.0	pK_i	63
⤷	pK_i <5.0 (K_i >1x10^-5 M) [63]
MRS5151		Mm	Agonist	5.0	pK_i	99
⤷	pK_i 5.0 (K_i 1.05x10^-5 M) [99]
MRS5151		Hs	Agonist	4.8	pK_i	99
⤷	pK_i 4.8 (K_i 1.49x10^-5 M) [99]
binodenoson		Hs	Agonist	4.3	pK_i	63
⤷	pK_i 4.3 (K_i 4.8x10^-5 M) [63]
capadenoson		Hs	Partial agonist	10.0	pEC₅₀	2
⤷	pEC₅₀ 10.0 (EC₅₀ 1x10^-10 M) [2]
neladenoson		Hs	Partial agonist	10.0	pEC₅₀	98
⤷	pEC₅₀ 10.0 (EC₅₀ 1x10^-10 M) [98]
MRS7469		Hs	Agonist	-	-	139
⤷	[139]

View species-specific agonist tables

Agonist Comments

The role for adenosine as endogenous ligand for the A1 receptor is described in [37] and [38].

The role for adenosine as endogenous ligand for the A₁ receptor is described in [38] and [39].

Capadenoson and neladenoson have been evaluated in phase 2 clinical trials for heart failure, but failed to meet expectations [149].

Primary target mapping: we have tagged the adenosine A₁ receptor as the primary target for this endogenous ligand as the affinity is marginally higher at this receptor isoform. However, adenosine is likely to exert clinical effects via other adenosine receptor family members.

Antagonists

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Ligand		Sp.	Action	Value	Parameter	Reference
[³H]DPCPX		Hs	Antagonist	8.4 – 9.2	pK_d	22,35,78,112,120,140
⤷	pK_d 8.4 – 9.2 (K_d 1.2x10^-9 – 6x10^-10 M) [22,35,78,112,120,140]
xanthine amine congener		Hs	Antagonist	7.5	pK_d	36
⤷	pK_d 7.5 [36]
PSB36		Rn	Antagonist	9.9	pK_i	1
⤷	pK_i 9.9 (K_i 1.24x10^-10 M) [1]
DPCPX		Rn	Antagonist	9.0 – 9.7	pK_i	74,79,151
⤷	pK_i 9.0 – 9.7 (K_i 1x10^-9 – 1.8x10^-10 M) [74,79,151]
CPFPX		Rn	Antagonist	9.2	pK_i	57
⤷	pK_i 9.2 (K_i 6.3x10^-10 M) [57]
LUF5981		Hs	Antagonist	9.1	pK_i	17
⤷	pK_i 9.1 (K_i 9x10^-10 M) [17]
derenofylline		Hs	Antagonist	9.0	pK_i	68
⤷	pK_i 9.0 (K_i 1x10^-9 M) [68]
FR194921		Hs	Antagonist	8.9	pK_i	93
⤷	pK_i 8.9 [93]
CPFPX		Hs	Antagonist	8.9	pK_i	57
⤷	pK_i 8.9 (K_i 1.26x10^-9 M) [57]
tonapofylline		Rn	Antagonist	8.9	pK_i	73
⤷	pK_i 8.9 (K_i 1.3x10^-9 M) [73]
rolofylline		Rn	Antagonist	7.9 – 9.7	pK_i	115
⤷	pK_i 7.9 – 9.7 (K_i 1.26x10^-8 – 1.9x10^-10 M) [115]
WRC-0571		Hs	Antagonist	8.8	pK_i	96
⤷	pK_i 8.8 [96]
rolofylline		Hs	Antagonist	8.1 – 9.1	pK_i	73,115
⤷	pK_i 8.1 – 9.1 (K_i 8x10^-9 – 7.2x10^-10 M) [73,115]
derenofylline		Rn	Antagonist	8.6	pK_i	68
⤷	pK_i 8.6 (K_i 2.51x10^-9 M) [68]
CGS 15943		Hs	Antagonist	8.5	pK_i	112
⤷	pK_i 8.5 (K_i 3.5x10^-9 M) [112]
DPCPX		Hs	Antagonist	7.4 – 9.2	pK_i	25,60,110,120,151
⤷	pK_i 7.4 – 9.2 (K_i 3.98x10^-8 – 6.3x10^-10 M) [25,60,110,120,151]
CGS 15943		Rn	Antagonist	8.2	pK_i	89
⤷	pK_i 8.2 (K_i 6.4x10^-9 M) [89]
tonapofylline		Hs	Antagonist	8.1	pK_i	73
⤷	pK_i 8.1 (K_i 7.4x10^-9 M) [73]
MRS1754		Rn	Antagonist	7.8	pK_i	75
⤷	pK_i 7.8 (K_i 1.68x10^-8 M) [75]
8-cyclopentyltheophylline		Hs	Antagonist	7.5 – 8.0	pK_i	22
⤷	pK_i 7.5 – 8.0 [22]
FK-453		Hs	Antagonist	7.7	pK_i	63
⤷	pK_i 7.7 (K_i 1.8x10^-8 M) [63]
xanthine amine congener		Hs	Antagonist	7.6	pK_i	64
⤷	pK_i 7.6 [64]
DU172		Hs	Antagonist	7.4	pK_i	49
⤷	pK_i 7.4 [49]
vipadenant		Hs	Antagonist	7.2	pK_i	46
⤷	pK_i 7.2 (K_i 6.8x10^-8 M) [46]
ST-1535		Hs	Antagonist	7.1	pK_i	102
⤷	pK_i 7.1 (K_i 7.18x10^-8 M) [102]
imaradenant		Hs	Antagonist	6.8	pK_i	12
⤷	pK_i 6.8 (K_i 1.6x10^-7 M) [12] Description: Binding affinity of AZD4635 determined in a radioligand binding competition assays with membranes prepared from CHO cells stably expressing human A1R.
MRE 2029F20		Hs	Antagonist	6.7	pK_i	7,144
⤷	pK_i 6.7 [7,144]
istradefylline		Rn	Antagonist	6.6	pK_i	39
⤷	pK_i 6.6 (K_i 2.3x10^-7 M) [39]
AS70		Hs	Antagonist	6.6	pK_i	144
⤷	pK_i 6.6 [144]
AS100		Hs	Antagonist	6.5	pK_i	144
⤷	pK_i 6.5 [144]
ATL802		Hs	Antagonist	6.4	pK_i	75
⤷	pK_i 6.4 (K_i 3.69x10^-7 M) [75]
MRS1754		Hs	Antagonist	6.4	pK_i	75
⤷	pK_i 6.4 (K_i 4.03x10^-7 M) [75]
PSB-11		Rn	Antagonist	6.4	pK_i	113
⤷	pK_i 6.4 (K_i 4.4x10^-7 M) [113]
ZM-241385		Hs	Antagonist	6.1 – 6.6	pK_i	63,112
⤷	pK_i 6.1 – 6.6 [63,112]
MRS928		Rn	Antagonist	6.3	pK_i	72
⤷	pK_i 6.3 [72]
L-97-1		Hs	Antagonist	6.2	pK_i	110
⤷	pK_i 6.2 [110]
MRS1041		Rn	Antagonist	6.2	pK_i	72
⤷	pK_i 6.2 [72]
SCH 58261		Hs	Antagonist	6.1 – 6.3	pK_i	63,112,140
⤷	pK_i 6.1 – 6.3 [63,112,140]
mefloquine		Hs	Antagonist	6.2	pK_i	150
⤷	pK_i 6.2 (K_i 6.75x10^-7 M) [150] Description: Binding affinity determined by displacement of [³H]-DPCPX from human A₁ receptors by increasing concentrations of racemic mefloquine.
AS99		Hs	Antagonist	6.1	pK_i	144
⤷	pK_i 6.1 [144]
galangin		Rn	Antagonist	6.1	pK_i	72
⤷	pK_i 6.1 [72]
LUF7602		Hs	Antagonist	6.1	pK_i	157
⤷	pK_i 6.1 (K_i 7.94x10^-7 M) [157] Description: Affinity determined from the displacement of specific [³H]DPCPX binding on CHO cell membranes stably expressing human adenosine A₁ receptors at 25 °C during 2 h of incubation.
PSB-10		Rn	Antagonist	6.1	pK_i	107
⤷	pK_i 6.1 (K_i 8.05x10^-7 M) [107]
istradefylline		Hs	Antagonist	6.1	pK_i	39
⤷	pK_i 6.1 (K_i 8.41x10^-7 M) [39]
MSX-2		Rn	Antagonist	6.1	pK_i	125
⤷	pK_i 6.1 (K_i 9x10^-7 M) [125]
MRS1042		Rn	Antagonist	6.0	pK_i	72
⤷	pK_i 6.0 [72]
preladenant		Hs	Antagonist	<6.0	pK_i	104
⤷	pK_i <6.0 (K_i >1x10^-6 M) [104]
MRE 3008F20		Hs	Antagonist	5.9 – 6.0	pK_i	63,144-145
⤷	pK_i 5.9 – 6.0 [63,144-145]
SCH442416		Hs	Antagonist	5.9	pK_i	63
⤷	pK_i 5.9 (K_i 1.11x10^-6 M) [63]
PSB-11		Hs	Antagonist	5.8	pK_i	113
⤷	pK_i 5.8 (K_i 1.64x10^-6 M) [113]
PSB-10		Hs	Antagonist	5.8	pK_i	113
⤷	pK_i 5.8 (K_i 1.7x10^-6 M) [113]
KF26777		Hs	Antagonist	5.7	pK_i	121
⤷	pK_i 5.7 (K_i 1.8x10^-6 M) [121]
CVT-6883		Hs	Antagonist	5.7	pK_i	33
⤷	pK_i 5.7 (K_i 1.94x10^-6 M) [33]
MRS1093		Rn	Antagonist	5.7	pK_i	72
⤷	pK_i 5.7 [72]
PSB1115		Rn	Antagonist	5.7	pK_i	106
⤷	pK_i 5.7 (K_i 2.2x10^-6 M) [106]
MRS1132		Rn	Antagonist	5.6	pK_i	72
⤷	pK_i 5.6 [72]
MSX-2		Hs	Antagonist	5.6	pK_i	125
⤷	pK_i 5.6 (K_i 2.5x10^-6 M) [125]
LAS38096		Hs	Antagonist	5.6	pK_i	32,146
⤷	pK_i 5.6 (K_i 2.821x10^-6 M) [32,146]
flavone		Rn	Antagonist	5.5	pK_i	72
⤷	pK_i 5.5 [72]
isobutylmethylxanthine		Hs	Antagonist	5.1	pK_i	64
⤷	pK_i 5.1 [64]
sakuranetin		Rn	Antagonist	5.1	pK_i	72
⤷	pK_i 5.1 [72]
theophylline		Hs	Antagonist	4.9 – 5.2	pK_i	35,64,78,144
⤷	pK_i 4.9 – 5.2 [35,64,78,144]
ATL802		Mm	Antagonist	5.0	pK_i	75
⤷	pK_i 5.0 (K_i 9.583x10^-6 M) [75]
MRS1191		Hs	Antagonist	<5.0	pK_i	85
⤷	pK_i <5.0 (K_i >1x10^-5 M) [85]
MRS1523		Hs	Antagonist	<5.0	pK_i	85
⤷	pK_i <5.0 (K_i >1x10^-5 M) [85]
VUF5574		Rn	Antagonist	>5.0	pK_i	143
⤷	pK_i >5.0 (K_i <1x10^-5 M) [143]
PSB603		Hs	Antagonist	<5.0	pK_i	13
⤷	pK_i <5.0 (K_i >1x10^-5 M) [13]
PSB603		Rn	Antagonist	<5.0	pK_i	13
⤷	pK_i <5.0 (K_i >1x10^-5 M) [13]
PSB1115

A1 receptor

Contents:

A₁ receptor