Pegylation Prevents Phospho-Ibuprofen Hydrolysis

Previous studies in rats and monkeys have shown that b2selective nicotinic acetylcholine receptor (nAChR) agonists reduce L-Dopa–induced dyskinesias (LIDs). Because rodent studies also suggested an involvement of a7 nAChRs in LIDs, the authors tested the effect of the potent, selective a7 agonist, ABT-107 [5-(6[(3R)-1-azabicyclo[2.2.2]oct-3-yloxy] pyridazin-3-yl)-1H-indole]. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-lesioned monkeys were gavaged with L-Dopa/carbidopa twice daily, which resulted in stable LIDs. Oral administration of ABT107 then decreased LIDs by 40–60%. The LIDs returned to control levels only after a 6-week ABT-107 washout, suggesting long-term molecular changes were involved. There was no effect of ABT-107 on Parkinsonism or cognitive performance. The authors next tested ABT-107 together with the b2 agonist, ABT-894 [(3-(5,6-dichloro-pyridin-3-yl)-1(S),5(S)-3,6-diazabicyclo [3.2.0]heptane], previously shown to reduce LIDs inParkinsonian monkeys. The effect of combined treatment on LIDs was similar to that with either drug alone. Thus, a7 and b2 nAChR–selective drugs may function via a final common mechanism to reduce LIDs.