David C. Remy

Chapter 2. Antipsychotic Agents and Dopamine Agonists

Publisher Summary With respect to the DA theory of schizophrenia, arguments have recently been presented that increased dopaminergic transmission produces positive symptomatology of schizophrenia (Type I syndrome, equivalent to an acute state of the disease), while other factors, such as structural changes in the brain, produce the negative symptomatology of schizophrenia (Type II syndrome, equivalent to the defect state of chronic sd1izophrenia). Research in Parkinsons disease, wherein the degeneration of DA neurons in the nigrostriatal pathway results in a pathological DA deficiency, continues to center on the therapeutic use of directly acting DA agonists. Such agonists are also being studied in schizophtenic patients as alternatives to conventional neuroleptic drugs. Moreover, a selective presynaptic DA receptor agonist may have the beneficial effect of a reduced potential for extrapyramidal side effects and tardive dyskinesia. The D-1 (linked to adenylate cyclase) and D-2 (not linked to adenylate cyclase) DA receptor classification of Kebabian and Calne remains the most widely accepted of the DA receptor concepts, and the nature of these receptors has been further characterized. Attention has continued to focus on the dopaminergic attributes of 2-aminotetralin derivatives. The nature and number of nuclear substituent, as well as their substitution pattern and the nature of substituent on the nitrogen atom, greatly influence the pharmacological profiles of such compounds by affecting their regional distribution and locus of action.