ABSTRACT
The most common hypokinetic disorder, Parkinson's disease (PD), causes a 4–7 Hz tremor, especially of limbs, which reduces with intentional activity, an increase in muscle tone, rigidity of all limb muscles, a difficulty in initiating movements and movements that are made are slow. The defining pathology of PD is the death of large numbers of neurons in the substantia nigra pars compacta (SNpc) that give rise to the nigrostriatal pathway. Bilateral destruction of the SNpc in monkeys with the neurotoxin 6-hydroxy dopamine causes rigidity and bradykinesia but not tremor. The chance discovery in 1982 that an illicitly manufactured pyridine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin caused very severe PD in a group of heroin addicts who ingested it, has led to a useful animal model of PD. 1-3,4-dihydroxyphenylalanine is effective in the early years of treatment but becomes less so with long-term treatment and 80% of patients develop dyskinesia, a hyperkinetic disorder, which resembles the motor dysfunction of Huntington's disease.
