TABLE 2

Pharmacological selectivity of A-740003

All assays were conducted at CEREP (http://www.cerep.fr/cerep/users/pages/catalog/assay/catalog.asp) using previously published methods (CEREP, Poitiers, France).

Target Ligand ∼IC50 Target Ligand ∼IC50
μM μM
Adenosine A1 [3H]DPCPX >10 Angiotensin (AT1) [125I][Sar1,Ile8]-ATII >10
Adenosine A2A [3H]CGS 21680 >10 Angiotensin (AT2) [125I]CGP 42112A >10
Adenosine A3 [125I]AB-MECA >10 Bombesin [125I][Tyr4]bombensin >10
Adrenergic α1 [3H]Prazosin >10 Bradykinin B2 [3H]NPC 17731 >10
Adrenergic α2 [3H]RX 821002 >10 CCKA [3H]Devazepide >10
Adrenergic β1 [3H](-)CGP-12177 >10 CCKB [3H]CCK-8 >10
Adrenergic β2 [3H](-)CGP-12177 >10 Endothelin (ETA) [125I]Endothelin-1 >10
ANP [125I]ANP >10 Endothelin (ETB) [125I]Endothelin-1 >10
Cannabinoid CB1 [3H]Win 55212-2 >10 Galanin (GAL1) [125I]Galanin >10
Cannabinoid CB2 [3H]Win 55212-2 >10 PDGF [125I]PDGF BB >10
Dopamine D1 [3H]SCH23390 >10 Melatonin (ML1) [125I]Iodomelatonin >10
Dopamine D2 [3H]Spiperone >10 Neurokinin (NK1) [125I][Sar9,Met(O2)11]-S >10
Dopamine D3 [3H]Spiperone >10 Neurokinin (NK2) [125I]NKA >10
Dopamine D4.4 [3H]Spiperone >10 Neurokinin (NK3) [125I][MePhe7]-NKB >10
Dopamine D5 [3H]SCH23390 >10 Neuropeptide Y1 [125I]peptide YY >10
GABA [3H]GABA >10 Neuropeptide Y2 [125I]peptide YY >10
IL-8B (CXCR2) [125I]IL-8 >10 Neurotensin (NT1) [125I]Neurotensin >10
TNFα [125I]TNFα >10 Somatostatin [125I]Tyr11-somatostatin >10
CCR1 [125I]MIP-1α >10 VIP1 (VPAC1) [125I]VIP >10
Histamine H1 [3H]Pyrilamine >10 Vasopressin V1a [3H]AVP >10
Histamine H2 [125I]APT >10 NE transporter [3H]Nisoxetine >10
Muscarinic M1 [3H]Pirenzepine >10 DA uptake [3H]GBR12935 >10
Muscarinic M2 [3H]AF-DX384 >10 Benzodiazepine central [3H]Flunitrazepam >10
Muscarinic M3 [3H]4-DAMP >10 Benzodiazepine peripheral [3H]PK11195 5
Muscarinic M4 [3H]4-DAMP >10 AMPA [3H]AMPA >10
Muscarinic M5 [3H]4-DAMP >10 Kainate [3H]Kainic acid >10
Opioid δ2 [3H]DADLE >10 NMDA [3H]CGP 39653 >10
Opioid κ [3H]U-69593 >10 Ca2+ channel DHP site [3H]PN200-110 >10
Opioid μ [3H]DAMGO >10 Ca2+ channel diltiazem site [3H]Diltiazem >10
ORL1 [3H]Nociceptin >10 Ca2+ channel verapamil site [3H]D 888 >10
PACAP PAC1 [3H]PACAP1-27 >10 Ca2+ channel N [125I]ω-Conotoxin >10
P2X [3H]α,βMeATP >10 K+ channel (voltage dependent) [125I]Dendrotoxin >10
P2Y [35S]dATPαS >10 K+ channel (Ca2+ dependent) [125I]Apmin >10
Serotonin 5-HT1A [3H]8-OH-PAT >10 Na+ channel (site 2) [3H]Batrachotoxinin >10
Serotonin 5-HT1B [3H]CYP >10 Cl- ionophore [35S]TBPS] >10
Serotonin 5-HT2A [3H]Ketanserin >10 Glycine (strychnine sensitive) [3H]Strychnine >10
Serotonin 5-HT2C [3H]Mesulergine >10 Glycine (strychnine insensitive) [3H]MDL105,519 >10
Serotonin 5-HT3 [3H]BRL 43694 >10 MAO-A [3H]Ro41-1049 >10
Serotonin 5-HT5A [3H]LSD >10 MAO-B [3H]Ro-19-6327 >10
Serotonin 5-HT6 [3H]LSD >10 σ [3H]DTG >10
Serotonin 5-HT7 [3H]LSD >10 σ2 [3H]DTG >10
σ1 [3H]Pentazocine >10
  • ANP, atrial natriuretic peptide; PACAP, pituitary adenylyl cyclase-activating protein; DPCPX, 8-cyclopentyl-1,3-dipropylxanthine; CGS 21680, 2-[p-(2-carboxyethyl)phenethylamino]-5′-N-ethylcarboxamidoadenosine; AB-MECA, 4-aminobenzyl-5′-N-methylcarboxamidoadenosine; RX 821002, 2-(2-methoxy-1,4-benzodioxan-2yl)-2-imidazoline; CGP-12177, 4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one; SCH23390, R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 4-DAMP, 4-diphenylacetoxy-N-methylpiperidine; DADLE, [d-Ala2, d-Leu5]-enkephalin; U-69593, (+)-(5α, 7α, 8β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]benzeneacetamide; DAMGO, [d-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin; MeATP, methylene-ATP; 8-OH-DPAT, 8-hydroxy-2-dipropylaminotetralin; CYP, cyanopindolol; LSD, d-lysergic acid diethylamide; CCK, cholecystokinin; PDGF, platelet-derived growth factor; NE, norepinephrine; DA, dopamine; AMPA, α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-d-aspartate; DHP, dihydropyridine; MAO, monoamine oxidase; VIP, vasoactive intestinal peptide; AVP, arginine vasopressin; GBR12935, (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)-piperazine); PK11195, 1-(2-chloro-phenyl)-N-methyl-N-(1-methylpropyl)-1-isoquinoline carboxamide; TBPS, t-butylbicyclophosphorothionate; CCR, chemokine receptor; ORL, opioid receptor-like; MIP, macrophage inflammatory protein; APT, aminopotentidine; VPAC, (vasoactive intestinal peptide) pituitary adenylate cyclase-activating peptide receptor; DTG, 1,3-di-o-tolyguanidine; WIN 55212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo-[1,2,3-d,e]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone; AF DX384, 5,11-dihydro-11-[2-(-[8-dipropylamino)methyl]-1-piperidinyl]-ethyl]amino]-carbonyl-6H-pyrido[2,3-b] [1,4]benzodiazepin-6-one; BRL 43694, granisetron; MDL 105,519, (E)-3-(2-phenyl-2-carboxylethenyl)-4,6-dichloro-1[3H]-indole-2-carboxylic acid; NPC 17731, d-Arg[Hyp3, d-HypE- (transprolyl)7,Oicc8]bradykinin; Ro41-1049, N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide HCl; CGP 39653, d,l-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid; CGP 42112A, N-α-nicotinoyl-Tyr-(N-α-CBZ-Arg)-Lys-His-Pro-Ile-OH; D 888, verampil derivative; PN200-110, (+)-[3H]isopropyl-4-(2,1,3-benzoxadiazol-4-yl)-1,4,-dihydro-5-methoxycarbonyl-2,6-dimethyl-3-pyridinecarboxylate; Ro 19-6327, lazabemide..