Extrapyramidal motor system, involvement

Adverse Neurological Effects Many neurological syndromes, particularly involving the extrapyramidal motor system, occur following the use of most antipsychotic drugs, especially with the high-potency D -receptor antagonists (tricyclic piperazines and butyrophenones). Acute adverse extrapyramidal effects are less likely with aripiprazole, clozapine, quetiapine, thioridazine, and ziprasidone, or low doses of olanzapine or risperidone. 

Parkinsonism is associated with a number of degenerative changes in both the structure and the chemistry of the basal ganglia. The relationship between the symptoms of the disease and these changes is dependent upon what is the normal function in the extrapyramidal motor system of such substances as dopamine, noradrenaline, serotonin, and the melanins, as well as others such as acetylcholine whose levels appear to be normal in Parkinsonism. Nevertheless, normal levels do not exclude disordered function since dynamic systems can involve different rates of turnover with no apparent change in concentrations. Synaptic transmission in the central nervous system has been extensively reviewed [59-61] and only those factors relevant to Parkinsonism will be discussed here. 

Laudanosine (6,7,3, 4 -tetramethoxy-1 -benzyltetrahydroisoquinoline) was isolated for the first time by Hesse (371) from opium. Intravenous administration of this substance to rabbits reduced the intraocular pressure (372). The whole effect manifested itself by motor restlessness, convulsions, disorders in coordination of movements, salivation, etc., which indicated an involvement of the extrapyramidal system and the mesencephalon. The effect produced by synthetic racemic laudanosine on rabbits was similar to that of the (+) form, but it was more toxic (373). The pharmacological properties of laudanosine have also been described (374). 

Polyneuropathy with both sensory and motor involvement is much more common among cancer patients than pure SN [83, 110, 111]. SCLC is the most common associated tumor, although other solid tumors may be found [112]. Sensory-motor neuropathy is a quite common paraneoplastic feature in patients with onconeural antibodies, especially Hu and CRMP-5 antibodies. The CRMP-5 antibody is particularly associated with SCLC and thymoma [30]. The CRMP-5 antibody binds to oligodendrocytes as well as to neurons in specific brain regions and the retina and Schwann cells of the peripheral nervous system. In accordance with this, the clinical characteristics are heterogeneous. Many patients exhibit mixed axonal and demye-linating sensory-motor neuropathy, optic neuritis, or cerebellar dysfynction [85, 113], as well as extrapyramidal symptoms (Chapter 5.3). 

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