Posted by SLS on March 8, 2002, at 7:13:22
In reply to Re: Buspar reduces serotonin, posted by Frankie on March 7, 2002, at 20:47:05
I thought the following article appearing on Medscape would be helpful along this thread. Please forgive me if my posts are little more than copy-and-paste. It might be worth noting that buspirone and its sister drugs, gepirone, and ipsapirone, are serotonin 5-HT1a autoreceptor agonists (partial). Here, buspirone is acting like "fake" serotonin at the same site that the article describes as needing to be downregulated for SSRIs to exert their therapeutic antidepressant effects. Perhaps some neurons need an extra kick in the ass. This might account for buspirone's reputation as being effective as an augmentor of antidepressants, but not in monotherapy. It occurs to me that a full 5-HT1a antagonist like pindolol would mask these autoreceptors and thus virtually "downregulate" them and produce the desired dynamics prior to the two week latency necessary for this to occur naturally. This might account for pindolol's reputation as being able to accelerate antidepressant response.
Understanding What Antidepressants Dohttp://www.medscape.com/viewarticle/418726
- Scott
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<excerpt>Understanding What Antidepressants Do
"Pierre Blier, MD, PhD, of the University of Florida at Gainesville discussed the biological effects of antidepressant molecules on neurotransmitters and receptors. He began by looking closely at selective serotonin reuptake inhibitors (SSRIs) and how these drugs impact the serotonin system.[4]
Dr. Blier reviewed the regulation of the brain's serotonin system. The cell bodies of the serotonin neurons are located in the brainstem, mostly in the median and dorsal raphe nuclei. Projections from these two nuclei reach multiple brain structures. He illustrated the activities of the serotonin (5-HT)-1A autoreceptor and the 5-HT uptake transporter. He explained that when the 5-HT-1A receptor is stimulated by an increase in the amount of serotonin, it will decrease the firing activity of the serotonin neurons.
When an SSRI is introduced, initially there is an increase in serotonin levels at the cell body due to blockade of the 5-HT uptake transporter. The 5-HT-1A autoreceptors are stimulated and decrease the firing frequency of the neuron. Yet, at the level of the synaptic bouton, there is no marked increase in serotonin availability, even though the transporters are inactive, because the firing activity reaching the terminals is decreased. However, after a few weeks of treatment with the SSRI, the autoreceptors are desensitized and allow a recovery of firing activity. At the synaptic bouton, reuptake is still blocked, firing activity is restored, and there is more serotonin because the terminal autoreceptors are desensitized. This allows 5-HT neurons to release their transmitters without negative feedback action in the presence of reuptake inhibition. The time necessary to obtain these adaptive changes is consistent with the delayed onset of action of SSRIs in major depression."
poster:SLS
thread:95230
URL: http://www.dr-bob.org/babble/20020307/msgs/97029.html