Central nervous system depressants, e.g. alcohol, barbiturates, and benzodiazepines, have a wide spectrum of activity in human and animals. These depressants produce varying degrees of CNS depression, depending mainly upon the dose used. In small doses, they can alleviate anxiety and/or reduce spontaneous activity; in moderate doses, they induce sleep; with large doses, severe CNS depression progresses to anesthesia, coma or even death. This graded, dose-dependent CNS depression is a common feature of these agents. In addition to causing CNS depression, these agents also possess other pharmacological properties, e. g. muscle relaxation, Anticonvulsant activity, respiratory depression, hypothermia, etc. Tolerance-dependence developing to sedative-hypnotics is a common feature following continuous administration of sedative-hypnotics. Tolerance is defined as a decreasing response to repeated administration of the same dose of a sedative-hypnotic or as a necessary increase of the dosage to obtain the initial response. There are two types of tolerance-one dispositional (pharmacokinetic), the other functional (pharmacodynamic). Dependence is defined as a modification of physiological functions that require continuous drug adiministration to prevent the appearance of withdrawal symptoms. Abrupt withdrawal from long-term usage of these drugs may produce anxiety, dizziness, nausea and vomiting, insomnia, muscular twitching, hyperthermia, delirium, tremors, convulsions, and death. Evidence accumulated suggests that some of the pharmacological actions exerted by sedative-hypnotics, e.g benzodiazepines, barbiturates and alcohol, may be mediated through the GABA system by mimicking GABAergic transmission. However, the mechanisms of the actions of these agents on the GABA system remain to be elucidated. Benzodiazepines have been demonstrated to have receptors which are parts of the GABAA receptors (GABA benzodiazepine receptor chloride ionophore complexes). Although a definitive barbiturate binding site has not yet been identified, the available evidence strongly suggests that barbiturate binding sites and convulsant binding sites are separate but allosterically affect each other. As far as ethanol is concerned, it is likely that multiple neurotransmitter systems are affected. Therefore, it is still unclear how alcohol, barbiturates, and benzodiazepines are functionally associated with the GABA system. The evidence summarized demonstrates that the GABA synapse plays an important role in the pharmacologic effects of barbiturates, alcohol and benzodiazepines. There are similarities and differences in the effects of these CNS depressants on the pharmacology and biochemistry of the GABA synapse. The effects of alcohol, barbiturates and benzodiazepines on GABA synapses are different in different brain regions. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in (a) animal models used, (b) brain regions used, (c) protocols used in treating the animals (dose, duration, form and route of administration, etc.) and/or (d) techniques used (pharmacological, biochemical, physiological, etc.)

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