Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.
L-Dopa plus carbidopa treatment remains the first-line therapy in Parkinson's disease. The use of catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO) inhibitors as an adjunct to L-dopa therapy has yielded varying degrees of success. Quercetin, a flavonoid present in many plants, is reported to inhibit COMT and MAO activities, the key enzymes involved in the metabolism of dopamine. In the present study we have studied the effect of quercetin on the L-dopa plus carbidopa combination against perphenazine and reserpine-induced catalepsy in rats. Neuroleptic-induced catalepsy is a widely accepted animal model for testing the drugs used in parkinsonism. Catalepsy in rats was induced by administration of perphenazine (5 mg/kg i.p.) or reserpine (2.5 mg/kg i.p.) + alpha-methyl-P-tyrosine (200 mg/kg i.p.). Catalepsy in animals was assessed by using the bar test. The quercetin dose (25-100 mg/kg, p.o.) dependently reversed perphenazine- as well as reserpine-induced catalepsy. When quercetin was combined with a subthreshold dose of L-dopa plus carbidopa, the anticatatonic effect was potentiated. Pretreatment with a central COMT inhibitor, 3,5-dinitrocatechol (OR-486) (10 mg/kg p.o.), or a MAO-B inhibitor, selegiline (5 mg/kg i.p.), also potentiated the actions of threshold dose of quercetin against perphenazine- or reserpine-induced catalepsy. On the other hand adenosine (100 mg/kg i.p.), which is known to decrease the release of catecholamines through an action on presynaptic A(1) receptors, partly reversed the protective effect of quercetin against perphenazine-induced catalepsy. Quercetin through its COMT and MAO enzyme-inhibiting properties might potentiate the anticatatonic effect of L-dopa plus carbidopa treatment. The results of the present study strongly suggest that quercetin could serve as an effective adjunct to L-dopa therapy in Parkinson's disease.
Singh
Amanpreet
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Naidu
Pattipati S
PS
Kulkarni
Shrinivas K
SK
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D065098:Catechol O-Methyltransferase Inhibitors; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use; D010546:Perphenazine / Q000633:toxicity; D011794:Quercetin / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000633:toxicity
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D008996:Monoamine Oxidase Inhibitors; D007980:Levodopa; D012110:Reserpine; D011794:Quercetin; D010546:Perphenazine