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Chapter 2. Anxiolytics, Anticonvulsants and Sedative-Hypnotics

1986; Elsevier BV; Linguagem: Inglês

10.1016/s0065-7743(08)61112-4

1557-8437

Michael Williams, Naokata Yokoyama,

Olfactory and Sensory Function Studies

Publisher Summary Public interest in anxiety has continued to increase, with over 13 million individuals in the United States being affected by this disorder. At the preclinical level, the emphasis has been on attempts to separate the various pharmacological actions of the benzodiazepines (i.e., anxiolytic, sedative, anticonvulsant, and muscle relaxant), into distinct processes mediated via different receptor subtypes, although this approach is more molecular than physiological. Concurrently based on the activity of buspirone and related compounds the mechanistic emphasis has switched to the role of serotonin in the etiology of anxiety. This chapter discusses Benzodiazepine receptor ligands—pyrazoloquinoline, CGS 9896, CGS 9895, β-CMC, SAS 646, the “hetrazepine,” brotizolam (WE 941), metaclazepam, (KC-2547), loflazepate (CM 6912), and some others. BZ receptor subtypes, peripheral BZ receptors, endogenous ligands, opiate and thyrotropin releasing hormone (TRH) receptor interactions have been detailed, also Serotonergic aspects of anxiety and the behavioral aspects—with the shift in focus from BZs to serotonergics and other factors—the classical conflict paradigms are proving to be inadequate as preclinical models of anxiety. As a result, acoustic startle, distress vocalization, aggression, brain stimulation reinforcement, and defense burying paradigms are undergoing evaluation, as are various neophobic models, including arm maze and open field behavior—sedative/hypnotics and anticonvulsants. A short note has been provided on some novel approaches to anxiety.