Adenosine A(2A) receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats

The effects of novel adenosine A(2A) receptor antagonists KF17837 ((E)-1,3- dipropyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione) and KW-6002 ((E)-1,3-diethyl-8-(3,4-dimethoxystyryl) -7-methyl-3,7-dihydro- 1H-purine-2,6-dione), on rotational behavior induced by apomorphine or L-DO PA (L-3,4-dihydroxyphenylalanine) were investigated in rats with unilateral 6-hydroxydopamine lesions. Both KF17837 and KW-6002 slightly induced rotat ional behavior per se. However, KF17837 and KW-6002 significantly increased the total counts of turning induced by apomorphine at doses of 3 mg/kg, p. o. and 10 mg/kg, p.o., and at doses of 1 mg/kg, p.o. and higher, respective ly. KF17837 and KW-6002 also potentiated the rotational behavior induced by L-DOPA at a dose of 3 mg/kg, p.o. Furthermore, i.c.v. injection (10 mug/20 yl) of a. selective adenosine A(2) receptor agonist CGS 21680 {2[p-(2-carb oxy-ethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine} partially prevent ed the rotational behavior induced by apomorphine and this inhibition was r eversed by KW-6002 (1 mg/kg, p.o.). The increase in total counts of apomorphine-induced turning by the adenosin e A,, receptor antagonists seems to be mainly attributable to prolongation of turning duration rather than enhancement of intensity. These results sug gest that these adenosine A, receptor antagonists may be useful to ameliora te shortening in the duration of dopaminergic drug response in patients wit h advanced Parkinson's disease. (C) 2000 Elsevier Science B.V. All rights r eserved.