Levodopa Donepezil

Small open-label pilot studies or challenge studies have been reported for the treatment of tics with various agents such as topiramate (Abuzzahab and Brown, 2001), levodopa (Black and Mink, 2000), low-dose naloxone (van Wattum et ah, 2000), donepezil (Hoopes, 1999), cyproterone (Izmir and Dursun, 1999), and ondansetron (Toren et ah, 1999). The safety and effectiveness of the chronic use of these agents, especially in children, requires more systematic studies. 

Donepezil 5 mg daily for 15 days eaused a modest 30% increase in the AUCq oflevodopa in a placebo-controlled study in 23 patients with Parkinson s disease taking levodopa/carbidopa. There was no change in car-bidopa pharmacokinetics, and the pharmacokinetics of donepezil did not differ between the patients with Parkinson s disease and a control group of healthy subjects. There was no obvious difference in adverse effects between patients with Parkinson s disease and the control subjects, and no evidence that donepezil significantly altered motor activity in those treat-... 

Parkinsonism is due to an imbalance between two neurotransmitters, dopamine and acetylcholine, in the basal ganglia of the brain. Centrally acting anticholinesterases increase the amount of acetylcholine in the brain, which could lead to an exacerbation of parkinsonian symptoms. Levodopa improves the situation by increasing the levels of dopamine. It is not known why donepezil modestly increased the levels of levodopa. 

Okereke CS, Kirby L, Kumar D, Cullen El, Pratt RD, Hahne WA. Concurrent adm inistration of donepezil HCl and levodopa/carbidopa in patients with Parkinson s disease assessment of pharmacokinetic changes and safety following multiple oral doses. Br J Clin Pharmacol (2004) 58 (Suppl 1) 41-9. 

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