U-95666E: a potential anti-parkinsonian drug with anxiolytic activity.
1. U-95666E, a D2 selective dopamine agonist, was investigated for its effect on rat striatal acetylcholine (ACh) concentration and the results were compared with those obtained with pergolide, pramipexole and bromocriptine under similar conditions. 2. U-95666E, pergolide, pramipexole and bromocriptine dose-dependently increased striatal ACh concentration both in the non-reserpinized and reserpinized rats. 3. Intrinsic activity of U-95666E was similar to pergolide and pramipexole in non-reserpinized rats, but significantly lower in reserpinized rats. 4. The sensitivity of these dopamine agonists for increasing ACh levels in the denervated as compared to innervated striatum were significantly (p < 0.01) higher. 5. U-95666E also has anxiolytic activity in mice. 6. In conclusion, U-95666E may have potential for the treatment of Parkinson's Disease and associated anxiety.
Sethy
V H
VH
CNS Diseases Research, Pharmacia & Upjohn, Inc., Kalamazoo, MI, USA.
Ellerbrock
B R
BR
Wu
H
H
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003714:Denervation; D018491:Dopamine Agonists / Q000494:pharmacology*; D004597:Electroshock; D008297:Male; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013312:Stress, Physiological / Q000503:physiopathology; D013563:Sympathectomy, Chemical
D014151:Anti-Anxiety Agents; D000978:Antiparkinson Agents; D001562:Benzimidazoles; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; C108539:U 95666E; D006152:Cyclic GMP; D000109:Acetylcholine