Currently the only P2Y receptor subtype targeted by drugs in clinical use i
s the P2T(AC) (or P2Y(12)) receptor, which has been recently cloned and is
only distantly related to other P2Y subtypes. It is believed that the activ
e metabolites of thienopyridine antithrombotic agents (ticlopidine, clopido
grel) bind covalently to that receptor and inactivate it in an irreversible
way. The same receptor is also the target of competitive antagonists deriv
ed from ATF: such as AR-C69931MX. Other subtypes also have potential as pha
rmacotherapeutic targets. The demonstration that P2Y(1)(-/-) mice have a de
fective platelet aggregation and increased resistance to thromboembolism su
ggests that P2Y(1) antagonists could constitute a new class of antithrombot
ic agents. Activation of the P2Y(2) receptor by aerosolized UTP and derivat
ives constitutes one strategy for the symptomatic treatment of cystic fibro
sis and other obstructive airway diseases. The study of P2Y(2)(-/-) mice su
ggests that P2Y(4) and P2Y(6) receptors might constitute additional targets
in that framework. P2Y(6) receptor antagonists might be useful in inflamma
tory bowel disease in view of their expression on activated T lymphocytes i
nfiltrating the lesions in patients. The P2Y(11) receptor mediates the stim
ulatory effect of ATP on the granulocytic differentiation of HL-60 promyelo
cytic leukemia cells, suggesting that P2Y(11) agonists might be useful in t
he treatment of some farms of neutropenia and leukemia. Drug Dev. Res. 52:1
87-189, 2001. (C) 2001 Wiley-Liss, Inc.