Effect of U-91356A, a potential anti-Parkinsonian drug, on striatal acetylcholine concentration

Antiparkinsonian drugs are dopamine agonists and they have been reported to increase striatal acetylcholine (ACh) concentrations. U-91356A is a D2 selective dopamine agonist. Therefore, it was investigated for its effect on rat striatal ACh concentration, and the results were compared 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 intrinsic 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 levels, and intrinsic activity of U-91356A (P < 0.01) was higher as compared to that obtained with quinpirole or pergolide. In the unilateral substantia nigra lesioned animals, the intrinsic activity of U-91356A for increasing striatal ACh was significantly (P < 0.01) higher in the denervated, as compared to innervated, striatum. The supersensitive response of quinpirole and pergolide for increasing striatal ACh was also observed on the lesioned as compared to intact side. Haloperidol significantly (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 D2 dopamine receptors and is expected to be an effective anti-parkinsonian drug. © 1996 Wiley-Liss, Inc.