Posted by Keith Talent on February 12, 2004, at 23:39:37
In reply to Tricyclic antidepressants queries, posted by irwind on February 12, 2004, at 17:25:37
> i am a little confused about some of the stuff i read about tricyclic antidepressants (TCA's).
> i am particualrly confused about their (TCA's)
> action on noradrenaline/norepinephrine.
> i have read that they (TCA's) work by increasing their amounts in the brain. but i also read as a
> side effect alpha-adrenolytic action it causes vasodilation and may cause hypotension.
> the two actions are exactly the opposite of each other.
> please it would be great if some one clarifies this for me.
> irwindThey work by blocking reuptake of noradrenaline (and serotonin in the case of clomipramine). This causes increased concentrations of noradrenaline in the synapses (chemical gaps that link nerve cells). For a while, there is increased agonism of receptors on the post-synaptic (downstream) side of the synapse. This then produces changes inside the post-synaptic neuron via biochemical cascades. The end result is a change in the rate of transcription of certain key genes, like that for brain-derived neurotrophic factor. Changes at this definitive level are believed to produce the antidepressant response, and also account for the delay of at least a fortnight. The statement that tricyclics increase the level of noradrenaline in the brain may not be at all true in overall terms, but there is an increase in synaptic concentration, possibly only for weeks while the downstream effects start to build.
Tricyclic have a side effect (to varying degrees) of blocking alpha-1 receptors. This causes postural hypotension, impotence, etc. I suppose this might interfere to some extent with the mechanism of beneficial action above.
poster:Keith Talent
thread:312558
URL: http://www.dr-bob.org/babble/20040210/msgs/312676.html