Posted by SLS on January 25, 2009, at 10:54:32
Seroquel (quetiapine) was approved by the FDA in 1997 for the treatment of schizophrenia. It has since shown itself to be effective for treating a broad range of other conditions, including:
Chronic Schizophrenia
Schizoaffective disorder
Bipolar mania
Bipolar depression
Mood stabilizer
Unipolar depression
Generalized Anxiety DisorderQuetiapine is known to be a dopamine D2 receptor antagonist and a 5-HT2a receptor antagonist. However, so are most of the other atypical neuroleptics. Yet they are not generally effective for all of these conditions. What's up?
Well, recently some scientists got smart and decided to test the major metabolite of quetiapine, norquetiapine. They found that it was a potent NE reuptake inhibitor (like desipramine or nortriptyline), a partial agonist at 5-HT1a receptors (like buspirone), and of particular interest, a 5-HT2c receptor antagonist. This receptor is thought to increase norepinephrine and dopamine neurotransmission in the prefrontal cortex, which is thought to be involved in depression.
Perhaps we have an answer as to why low dosages of Seroquel are soporific (sleep-inducing) and higher dosages are more alerting - NE reuptake inhibition. At low dosages, there isn't enough norquetiapine formed to produce the alerting NE reuptake inhibition. This allows for the other properties like its antihistaminergic and antidopaminergic effects to predominate. At high dosages, though, the metabolite, quetiapine collects and becomes high enough in concentration to potently inhibit NE reuptake, and thus supercede the hypnotic effects. The 5-HT2c antagonism probably acts synergistically and produces energizing effects as well.
Now, whenever we attempt to explain the clinical properties of Seroquel, we must also look at the actions of norquetiapine, its active metabolite.
- Scott
poster:SLS
thread:876047
URL: http://www.dr-bob.org/babble/20090104/msgs/876047.html