PHARMACOLOGY, BIOCHEMISTRY AND PHYSIOLOGY OF CENTRAL NEUROTRANSMITTERS

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1. The interval from the onset of symptoms to the introduction of levodopa was unrelated to the time from levodopa initiation to motor complication onset. There no longer appears to be a rational basis for delaying levodopa therapy in parkinsonian patients. 2. Motor response complications reflect striatal system changes due to dopaminergic deafferentation and intermittent dopaminomimetic treatment and tend to normalize with the more physiologic stimulation afforded by continuous replacement strategies. 3. Glutamatergic mechanisms affect extrapyramidal motor function: In rats, D-2 mediated responses require concurrent NMDA receptor stimulation, while D-1 receptor-regulated pathways have varying degrees of sensitivity to NMDA receptor blockade; the subthalamic nucleus contributes primarily to the expression of D-2 mediated motor behaviors. In patients with Parkinson's disease, glutamatergic stimulation with milacemide transiently increased overall parkinsonian severity, especially rigidity. 4. No generalized defect in mitochondrial respiratory function could be documented in Parkinson's disease: oxygen consumption rates and respiratory chain enzyme activities in platelets and muscle mitochondria as well as blood lactate levels following glucose loading did not differ significantly between patients and controls. 5. Tourette syndrome patients have marked decreases in ventral brain areas, increases along the superior cortical convexities, and inverted relationships between these limbic and sensorimotor cortical regions appear on PET-fluorodeoxyglucose scans. 6. Physostigmine by continuous intravenous infusion at maximum tolerated levels inhibits CSF acetylcholinesterase by only 21% and produces little cognitive benefit. Amnestic doses of the anticholinergic, scopolamine, increase cortical function in normal elderly subjects in contrast to the decreases, especially parietotemporal, in PET scans of Alzheimer patients. Physostigmine, rather than normalizing, marginally diminishes cortical metabolism.