EFFECT OF U-91356A, A POTENTIAL ANTI-PARKINSONIAN DRUG, ON STRIATAL ACETYLCHOLINE CONCENTRATION

Antiparkinsonion drugs are dopamine agonists and they have been report ed to increase striatal acetylcholine (ACh) concentrations. U-91356A i s a D-2 selective dopamine agonist. Therefore, it was investigated for its effect on rat striatal ACh concentration, and the results were co mpared with those obtained with pergolide and quinpirole under similar conditions. U-91356A was as potent as pergolide and less potent than quinpirole in increasing striatal ACh in non-reserpinized rats. The in trinsic activity of U-91356A was significantly (P < 0.03) greater than pergolide in non-reserpinized rats. In reserpinized rats, the potency of investigated dopamine agonists was similar for elevating ACh level s, and intrinsic activity of U-91356A (P < 0.01) was higher as compare d to that obtained with quinpirole or pergolide. In the unilateral sub stantia nigra lesioned animals, the intrinsic activity of U-91356A for increasing striatal ACh was significantly (P < 0.01) higher in the de nervated, as compared to innervated, striatum. The supersensitive resp onse of quinpirole and pergolide for increasing striatal ACh was also observed on the lesioned as compared to intact side. Haloperidol signi ficantly (P < 0.01) blocked U-91356A-induced elevation in striatal ACh in non-reserpinized rats. Based on these results, U-91356A appears to be a potent agonist of striatal post-synaptic D-2 dopamine receptors and is expected to be an effective anti-parkinsonian drug. (C) 1996 Wi ley-Liss, Inc.