PHARMACOLOGY, BIOCHEMISTRY AND PHYSIOLOGY OF CENTRAL NEUROTRANSMITTERS

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1. Motor response complications in patients with advanced Parkinson's disease appear largely attributable to nonphysiologic fluctuations in intrasynaptic dopamine. Continuous dopaminomimetic therapies limit these complications. 2. Studies of one prototypic dopamine agonist revealed an antiparkinsonian efficacy only half that of levodopa, despite an equal ability to induce dyskinesias. Since this drug acts main y on D dopamine receptors, agonist development will now focus on compounds, like levodopa, that lead to Dl as well as D2 dopamine receptor stimulation. 3. Striatal dopaminoceptive systems in an animal model of Parkinson's disease are differentially affected by chronic levodopa therapy and by the continuous or intermittent nature of the therapeutic regimen: Dl output through the striatonigral system decreases while D2 output through the striatopallidal pathway increases. Levodopa replacement, especially when given intermittently, thus does not simply reverse the effects of dopamine denervation but creates a new functional state differing from both the normal and denervated states that could contribute to motor complications. 4. Neuropsychologic studies compared cognitive deficits in patients with Alzheimer's disease with those in Parkinsonian patients with equally severe dementia: Semantic and episodic memory were impaired in both groups, but to a relatively greater degree in Alzheimer patients, while demented Parkinsonian patients were relatively more compromised on executive tasks.