Psycho-Babble Medication Thread 312558

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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.
irwind

 

Re: Tricyclic antidepressants queries » irwind

Posted by Chairman_MAO on February 12, 2004, at 22:15:03

In reply to Tricyclic antidepressants queries, posted by irwind on February 12, 2004, at 17:25:37

Tricyclics (except for trimipramine) block the NE reuptake pump with varying potencies, thereby increasing synaptic NE. They also block the a1-adrenergic receptor; the effect of this is that the cholinergic innervation dominates: vasodialation, etc. This is merely a specific antagonistic action at a specific receptor subtype, though; there are many other adrenergic receptors. Antidepressants are thought to work in part by downregulating BETA adrenoreceptors.

 

Re: Tricyclic antidepressants queries

Posted by irwind on February 12, 2004, at 23:13:48

In reply to Re: Tricyclic antidepressants queries » irwind, posted by Chairman_MAO on February 12, 2004, at 22:15:03

thank you for your clarification.
but i am still left feeling very confused about i am not a medical doctor just a lay person.
well if they block a1-adrenergic receptor they will counteract he effects of medications like modafinil - provigil.
just curious about one more thing like is it ok to take some nootropics which are specifically vasodilators - like nicergoline or hydergine when taking TCA's. i mean nicergoline is supposed to be a vasodilator that specifically has alpha-adrenolytic action. i mean will it counteract the antidepressant effect. any input will be appreciated. thank you chairman_MAO for your reply

 

Re: Tricyclic antidepressants queries

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.
> irwind

They 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.

 

Re: Tricyclic antidepressants queries

Posted by Chairman_MAO on February 13, 2004, at 7:29:53

In reply to Re: Tricyclic antidepressants queries, posted by Keith Talent on February 12, 2004, at 23:39:37

Does a1 blocking cause impotence? Vasodialation is key for erection, and I read one anecdotal report on here where Flomax, a selective a1 blocker, was used to correct urinary hesitancy and impotence on reboxetine.

I think it is important to note that we're really talking about a dose-dependent a1 ANTAGONISTIC action, not an absolute all-or-nothing "block". A good analogy here is that stimulants are still effective in treating ADHD when antipsychotics are used concurrently. Thus, even a1 agonists such as modafinil probably work along with TCAs; one might simply have to use higher doses.


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