Nitecapone and selegiline as effective adjuncts to L-DOPA in reserpine-induced catatonia in mice.
Reserpine-induced catatonia is a widely accepted animal model of Parkinson's disease. In the present study, reserpine (5 mg/kg i.p.) and alpha-methylpara-tyrosine (AMPT) (200 mg/kg i.p.) induced catatonia in mice 20 h and 1 h before the experiment, respectively, as assessed using the rota-rod and bar tests after reserpine treatment. There was a significant decrease in fall-off time in the rota-rod test and a significant increase in time spent on the bar in the bar test as compared to the untreated control mice. Combination therapy with L-DOPA (100 mg/kg i.p.) and carbidopa (10 mg/kg i.p.) was less effective in reversing catatonia as compared to higher doses of L-DOPA (200 mg/kg i.p.) and carbidopa (20 mg/kg i.p.), which showed intense hyperactivity in reserpinized mice. Pretreatment with nitecapone (30 mg/kg i.p.), a COMT inhibitor, or selegiline (10 mg/kg i.p.), a MAO-B inhibitor potentiated the motor stimulant actions of subthreshold doses of the L-DOPA (100 mg/kg i.p.) and carbidopa (10 mg/kg i.p.) combination. Amantadine (40 mg/kg i.p.), but not bromocriptine, potentiated the effects of L-DOPA treatment. The NMDA antagonistic action of amantadine may have beneficial effects. It is concluded that COMT and MAO-B enzymes play an important role in the metabolism of dopamine and administration of a COMT or MAO-B inhibitor may prove to be a better adjunct to L-DOPA therapy than a dopamine receptor agonist in Parkinson's disease.
Singh
A
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002389:Catatonia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D007274:Injections, Intraperitoneal; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010422:Pentanones / Q000627:therapeutic use*; D012110:Reserpine / Q000633:toxicity; D012642:Selegiline / Q000627:therapeutic use*; D019805:alpha-Methyltyrosine / Q000633:toxicity
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D010422:Pentanones; D012642:Selegiline; D007980:Levodopa; D019805:alpha-Methyltyrosine; D012110:Reserpine; C057364:nitecapone