[Recent progress in development of psychotropic drugs (3)--Antiparkinsonian agents applied in the treatment of Parkinson's disease or are under investigation for patients or model animals].
Tremor, akinesia, rigidity and postual instability are key signs of Parkinson's disease. The most important one is akinesia, which includes decreased spontaneous locomotor activity, slowness of movement, awkwardness and freezing. On the other hand, an electrical focal lesion in the brain, neurotoxin to dopaminergic neurons such as 6-hydroxydopamine (6-OHDA) or I-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), cholinomimetic tremorogenic agents such as oxotremorine or tremorine, monoamine depleting agents such as reserpine or tetrabenazine, or dopamine receptor antagonists such as haloperidol are applied to render animal parkinsonism. The estimation of locomotor activity can be done accurately in animal models. Tremor can be studied using the animals treated by cerebral focal lesion, neurotoxins or cholinomimetics. Skillfulness is hard to estimate in animals, however, it can be done in primates. Freezing appeared in patients with levodopa treatment over a long period. This is a specific motor sign in Parkinson's disease, and cannot be observed in animals. Supplementing dopamine by levodopa administration, retarding the metabolism of levodopa or dopamine by dopa decarboxylase inhibitor (DCI), monoamine oxidase inhibitor type B (MAO-B) inhibitor or catechol-O-methyltransferase (COMT) inhibitor, dopamine receptor agonists, anticholinergic agents, dopamine release enhancer/ uptake inhibitor, N-methyl-D-aspartate (NMDA) receptor antagonists, adenosine receptor antagonists, neurotrophic factors, GM1-ganglioside and nicotinic receptor agonists have been applied in the treatment of Parkinson's disease or are under investigation for patients. Agents to facilitate nerve growth or to inhibit the degeneration of nerves will be developed in the future.
Department of Pharmacology, Faculty of Medicine, Kagoshima University, Japan.
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D000818:Animals; D000978:Antiparkinson Agents; D018680:Cholinergic Antagonists; D004195:Disease Models, Animal; D015259:Dopamine Agents; D005677:G(M1) Ganglioside; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D010300:Parkinson Disease; D058915:Purinergic P1 Receptor Antagonists; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000978:Antiparkinson Agents; D018680:Cholinergic Antagonists; D015259:Dopamine Agents; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D058915:Purinergic P1 Receptor Antagonists; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D005677:G(M1) Ganglioside