Posted by ShawnThomas on August 3, 2007, at 19:15:29
In reply to Xanax/Klonopin chemcials?, posted by Sheilac on August 3, 2007, at 8:23:18
Yes, alprazolam (Xanax) and clonazepam (Klonopin) affect serotonin and dopamine systems in the brain. They do not directly affect these systems, but that does not imply that they lack indirect effects. Unfortunately, finding out what's happening to these systems and where in the human brain is no easy task. As a result, lab animals like rats are used, and measurements of the neurotransmitters and their metabolites are taken in different parts of their central nervous systems with a variety of methods. I like to use http://www.pubmed.gov and its MeSH or Medical Subject Headings Browser (http://www.ncbi.nlm.nih.gov/sites/entrez?db=mesh) to conduct searches for this sort of information. With the MeSH browser, I found that the MeSH term for the primary serotonin metabolite is "Hydroxyindoleacetic Acid"[Mesh] and the MeSH term for the primary dopamine metabolite is "Homovanillic Acid"[Mesh]. So you can perform a search like "Hydroxyindoleacetic Acid"[Mesh] AND clonazepam to find articles about how Klonopin affects serotonin metabolism. Note that you must always search for the generic name of a drug at PubMed.gov. You don't need to worry about finding a relevant MeSH term because that is done automatically for you when you search PubMed for a generic drug name.
If you want a detailed overview of the direct effect of these drugs, consider my comparison of benzodiazepines like Xanax and Klonopin and barbiturates like phenobarbital.
Barbiturates and benzodiazepines act at two different allosteric modulatory sites on gamma-aminobutyric acid type A (GABA-A) receptors. Because GABA-A receptors modulate chloride channels, barbiturates and benzodiazepines positively regulate the flow of chloride ions into neurons. The GABA-A receptor is a pentameric protein that may consist of a number of different combinations of subunits. The efficacy of these drugs at GABA-A receptors depends on the subunit compositions of the GABA-A receptor complexes that they bind to. The benzodiazepines have been found to bind to a subunit cleft on the GABA-A receptor surface located between the alpha and gamma subunits. Due to their lack of selectivity for receptor subtypes and increased efficacy, barbiturates are considered to be less safe than newer types of GABA-A modulatory drugs such as the benzodiazepines. Both drug types allosterically alter the shape of GABA-A receptors, which causes the receptors to exhibit a stronger affinity for GABA. Chloride channels in GABA-A receptor complexes exhibit at least three different open states that are characterized by their durations in milliseconds. Barbiturates increase the relative frequency of the occurrence of the longest open state and decrease the frequency of the occurrence of the shorter open states. On the other hand, benzodiazepines only increase the frequency that the channels will open into the shortest open state. Unlike benzodiazepines, barbiturates possess the ability to cause chloride channels in GABA-A receptor complexes to open in the absence of GABA. Some barbiturates may also affect other targets such as glycine channels, voltage-gated calcium channels, glutamate receptors, and nicotinic acetylcholine receptors; a few benzodiazepines might affect other targets as well.
Shawn
References:
Sigel E.
Mapping of the benzodiazepine recognition site on GABA(A) receptors.
Curr Top Med Chem 2002 Aug;2(8):833-9
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12171574&dopt=AbstractMehta AK, Ticku MK.
An update on GABAA receptors.
Brain Res Brain Res Rev 1999 Apr;29(2-3):196-217
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10209232&dopt=AbstractHevers W, Luddens H.
The diversity of GABAA receptors. Pharmacological and electrophysiological properties of GABAA channel subtypes.
Mol Neurobiol 1998 Aug;18(1):35-86
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9824848&dopt=AbstractDoble A.
New insights into the mechanism of action of hypnotics.
J Psychopharmacol 1999;13(4 Suppl 1):S11-20
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10667451&dopt=AbstractMacDonald RL, Rogers CJ, Twyman RE.
Barbiturate regulation of kinetic properties of the GABAA receptor channel of mouse spinal neurones in culture.
J Physiol. 1989 Oct;417:483-500.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=2482885Neil Harrison, Wallace B. Mendelson and Harriet de Wit
Barbiturates
Psychopharmacology - The Fourth Generation of Progress
http://www.acnp.org/g4/GN401000173/CH169.html
poster:ShawnThomas
thread:773708
URL: http://www.dr-bob.org/babble/20070730/msgs/773790.html