Posted by Scott L. Schofield on April 17, 2000, at 14:48:07
In reply to Re: SSRI's may not be so benign? - To Sean, posted by Sean on April 17, 2000, at 12:39:41
Dear Sean,
This is a great post.
I agree with you that it is not a good idea to extrapolate the observed phenomenology of tricyclics to the SSRIs.
I have a few questions for you. I am really not sure about this stuff - I am not trying to be argumentative.
> Well, here's what I understand (from Cooper, Bloom,
> and Roth's Biochemical Basic of Neuropharmacology):Has this book been written recently?
> - chronic presence of SSRI's decreases the responsiveness
> of the 5-HT1a autoreceptors and the function of
> terminal 5-HT autoreceptors. TCA's produce no
> observable change in these structuresAre these 5-HT1a autoreceptors presynaptic?
> - chronic presence of TCA's increases the responsiveness
> of the POST-synaptic 5-HT autoreceptorsWhat subtype of receptors are these?
Are they inhibitory? Are they somato-dendritic?
Are postsynaptic 5-HT1a autoreceptors inhibitory upon the induction of an action potential when stimulated?
Would this tend to reduce the activity of these pathways?
Do any other 5-HT receptor subtypes act as postsynaptic autoreceptors?
> In each case, net 5-HT neurotransmission is increased,
> so it is correct to say "TCA's affect serotonin."
> But the effect is produced by an observably different
> mechanism. ECT also increases the post-synaptic
> sensitivity of 5-HT receptors which is interesting
> in the sense that profound melancholia often responds
> to TCA's or ECT but not always SSRI's.> There is some evidence that TCA's with a substituted
> tertiary nitrogen (amitriptyline and imipramine)
> do directly bind reuptake in the way SRI's do, but
> not in the proportion or degree of the SRI's.How does the serotonin reuptake inhibition of chlomipramine (Anafranil) compare to the SSRIs in degree?
> I don't mean to be stiring things up here, but I
> simply do not accept the argument that historical
> experience with TCA's can be used as direct evidence that
> SSRI induced changes in neuron morphology are not
> worthy of some measured concern.I agree. Who said this anyway? This is silly.
> Perhaps what we should accept is that there is a
> degree of the unkown in psychopharmacology. Since
> the first generation of SSRI's were created, many
> subtypes of serotonin receptors have been discovered
> and cloned. Drugs which act preferentially to these
> subtypes may not have the same effects as the current
> generation of drugs. And then there are entire classes of
> neuropeptides which await exploration, so the current
> meds are like shifting, ephemeral frames in some
> movie about the story of our understanding of the
> brain. I think we're still in the first scene of
> the film...Oh yeah, big-time. But I am encouraged by what I see. Perhaps there is just a hint of light visible in the black box.
> As far as the "corscrew neurons" debacle, how would everybody
> feel if scientists did NOT explore the reasons
> behind it?What is this all about?
Thank-you for taking the time to post this stuff. I may have asked too many questions - sorry.
- Scott
poster:Scott L. Schofield
thread:29745
URL: http://www.dr-bob.org/babble/20000411/msgs/30355.html