0
0

Sections

Excerpt

Advances in the understanding of the pharmacological mechanisms mediating effects of sedative, hypnotic, and anxiolytic medications began with the discovery of the GABAA benzodiazepine receptor complex (Squires and Brastrup 1977), the predominant inhibitory receptor in the central nervous system. It is a ligand-gated ion channel, which is activated by the neurotransmitter GABA. Activation leads to increase in Cl ion influx into the neuron and hyperpolarization of the neuronal membrane. As a result, the threshold required for the excitatory neurotransmitter to depolarize the membrane and produce an action potential is increased (i.e., GABA inhibits "excitability" of neuronal membranes). The GABAA receptor has binding sites for GABA, as well as regulatory sites for benzodiazepines, barbiturates, neurosteroids, anesthetics, anticonvulsants, and ethanol (Mohler et al. 2002) (Figure 16–1). There is considerable evidence that all sedative-hypnotics and alcohol interact with the GABAA receptor and that inhalants that are subject to abuse (various volatile organic compounds present in fuels, solvents, and cleaning products) may have similar mechanisms (Whiting 2003). The exact neural mechanism of each class of sedative-hypnotics is not well understood, but considering the similarities in behavioral and physiological effects of these drugs, it is reasonable to assume that physiological dependence and abuse liability associated with these agents is related to the changes occurring in the GABAergic receptor system.

Your session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 16–1. Schematic representation of the GABAA receptor complex.(A) Each GABAA receptor contains five transmembrane subunits arranged in a circle around the channel. Many different subunits have been identified to date, which are grouped into several classes. Most receptors include two subunits, two subunits, and a , , , , or subunit (Mohler et al. 2002). (B) View from the extracellular space of the most commonly encountered receptor subtype with the location of the benzodiazepine and low-affinity GABA sites. This receptor has high affinity for benzodiazepines, mediating its sedative, amnestic, anticonvulsant, and reinforcing effects. It also has a high affinity site for flumazenil and zolpidem. BZ = benzodiazepine; Cl = chloride ion; GABA = -aminobutyric acid.
Table Reference Number
TABLE 16–2. Pharmacological effects associated with specific subunits and receptor subunit selectivity for specific pharmacological agents

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 6.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 7.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 11.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 4.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 12.  >
Psychiatric News
PubMed Articles
Cellular and behavioral interactions of gabapentin with alcohol dependence. J Neurosci 2008;28(22):5762-71.doi:10.1523/JNEUROSCI.0575-08.2008.
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation