Previous studies in rats and monkeys have shown that β2-selective nicotinic acetylcholine receptor (nAChR) agonists reduce L-Dopa–induced dyskinesias (LIDs). Because rodent studies also suggested an involvement of α7 nAChRs in LIDs, the authors tested the effect of the potent, selective α7 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 ABT-107 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 β2 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 in Parkinsonian monkeys. The effect of combined treatment on LIDs was similar to that with either drug alone. Thus, α7 and β2 nAChR–selective drugs may function via a final common mechanism to reduce LIDs.
See article at J Pharmacol Exp Ther 2014, 351:25–32.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics