Posted by den2 on July 11, 2003, at 22:33:34
Mirtazapine
As with all drugs, knowledge of the in vitro pharmacology of mirtazapine can help us understand its clinical pharmacology. Mirtazapine's most potent site of action is the histamine-1 receptor (Figure 1). At higher concentrations, the drug sequentially blocks the 5-HT2A receptor and then the alpha-2 adrenergic receptor (Figure 1). Although not illustrated in Figure 1, mirtazapine binds almost as avidly to the 5-HT2C and 5-HT3 receptors as it does to the 5-HT2A receptor.3,4
Doses of mirtazapine needed to treat clinical depression result in concentrations sufficient to block the 5HT2A, 5-HT2C, 5-HT3, and the alpha-2 adrenergic receptors. Higher concentrations (and hence doses) are obviously needed to block the alpha-2 adrenergic receptor site than are needed to block the serotonin receptors. These facts are consistent with the hypothesis that one or more of these mechanisms mediate the antidepressant efficacy of mirtazapine. This constellation of mechanisms of action is not shared by any other antidepressant, which raises the possibility that mirtazapine might work in patients who have not benefited from other types of antidepressants. There is some evidence supporting this possibility. Two separate studies have indicated that mirtazapine can work in patients who have not benefited optimally from treatment with amtriptyline11 or fluoxetine.12
If i read correctly on mirtazapines website..it says that alpha 2 antagonism starts at 15mgs. IT also says that higher doses are needed to block the alpha 2 receptor than is needed to block the 5ht2 5ht3 receptors. My question is ... dose it only take 7.5 mgs to block 5ht2 and 5ht3 receptors while not getting the alpha 2 antagonist effect until 15mgs?
poster:den2
thread:241050
URL: http://www.dr-bob.org/babble/20030708/msgs/241050.html