Drugs of Anti-Parkinson’s disease - 汕头大学医学院.pptVIP

Drugs of Anti-Parkinson’s disease Department of Pharmacology Zhang Yan-mei Pathogenesis of Parkinson’s disease Parkinson’s disease (PD) is a progressive disorder of movement that occurs mainly in the elderly. The chief symptoms are: Tremor at rest, usually starting in the hands (‘pill- rolling’ tremor), which tend to diminish during voluntary activity Pathogenesis of Parkinson’s disease Muscle rigidity, detectable as an increased resistance in passive limb movement --Bradykinesia Suppression of voluntary movements (hypokinesis), due partly to an inherent inertia of the motor system, which means that motor activity is difficult to stop as well as to initiate. Action of MPTP 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) causes irreversible destruction of nigrostriatal dopaminergic neurons in various species, and produces a PD-like state in primates. Parkinson’s Disease Degenerative disease of the basal ganglia causing tremor at rest, muscle rigidity hypokinesia, often with dementia. Often idiopathic, but may follow stroke, virus infection, can be drug-induced (neuroleptic drugs). Parkinson’s Disease Associated with marked loss of dopamine from basal ganglia. Can be induced by MPTP, a neurotoxin affecting dopamine neurons in the corpus striatum. Drugs Treatment of Parkinson’s Disease Drugs that replace dopamine (e.g. levodopa, usually used concomitantly with peripherally acting dopa decarboxylase inhibitor, e.g. carbidopa) Drugs that mimic the action of dopamine (e.g. bromocriptine, pergolide and others in development) Drugs Treatment of Parkinson’s Disease MAO-B inhibitors (e.g. selegiline) Drugs that release dopamine (e.g. amantadine) Acetylcholine antagonists (e.g. artane) Levodopa Mechanism: (1) Because dopamine does not cross the blood-brain barrier levodopa, the precursor of dopamine, is given instead. (2) Levodopa is formed L-tyrosine and is an intermediate in the synthesis of catecholamines. Levodopa Mechanism: (3) Levodopa itself has minimal p