Nitecapone and selegiline as effective adjuncts to L-DOPA in reserpine-induced catatonia in mice.

Abstract

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.

• Authors: A Singh, S K Kulkarni
• Journal: Methods and findings in experimental and clinical pharmacology (Methods Find Exp Clin Pharmacol) 2002 Jan-Feb Vol. 24 Issue 1 Pg. 23-9 ISSN: 0379-0355 [Print] Spain
• PMID: 11980384 (Publication Type: Journal Article)

Chemical References

• Antiparkinson Agents
• Catechol O-Methyltransferase Inhibitors
• Catechols
• Enzyme Inhibitors
• Pentanones
• Selegiline
• Levodopa
• alpha-Methyltyrosine
• Reserpine
• nitecapone

Topics

• Animals
• Antiparkinson Agents (therapeutic use)
• Catatonia (chemically induced, drug therapy, physiopathology)
• Catechol O-Methyltransferase Inhibitors
• Catechols (therapeutic use)
• Disease Models, Animal
• Drug Therapy, Combination
• Enzyme Inhibitors (therapeutic use)
• Female
• Injections, Intraperitoneal
• Levodopa (therapeutic use)
• Male
• Mice
• Motor Activity (drug effects)
• Pentanones (therapeutic use)
• Reserpine (toxicity)
• Selegiline (therapeutic use)
• alpha-Methyltyrosine (toxicity)