Novel ligands for P2 receptor subtypes in innervated tissues.
Among suramin analogues, the properties of P2 receptor subtype blockade and ecto-nucleotidase inhibition appear to be controlled by different structural parameters (Fig. 1 and 2, Table 1; Van Rhee et al., 1994; Beukers et al., 1995; Bültmann et al., 1996; Damer et al., 1998a, 1998b; and this study): the molecular size of the compounds, the position of the sulfonic acid residues in the naphthalene rings, the substitution pattern of the benzoyl moieties and the 3'- or 4'-aminobenzoyl-linkages of the phenyl rings "1" and "2". As a result, compounds with different receptor selectivity profiles were obtained. A maximum in potency at and selectivity for P2X1 receptors is reached in NF279, which is a specific P2 receptor antagonist and the compound with the highest P2X1 vs. P2Y receptor and ecto-nucleotidase selectivity presently available.
Lambrecht
G
G
Department of Pharmacology, Biocentre Niederursel, University of Frankfurt, Main, Germany. lambrecht@em.uni-frankfurt.de
Damer
S
S
Niebel
B
B
Czeche
S
S
Nickel
P
P
Rettinger
J
J
Schmalzing
G
G
Mutschler
E
E
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D007537:Isometric Contraction / Q000187:drug effects; D008024:Ligands; D008297:Male; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013498:Suramin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation / Q000502:physiology
D008024:Ligands; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D013498:Suramin; D000255:Adenosine Triphosphate