Posted by Sean on April 17, 2000, at 12:39:41
In reply to Re: SSRI's may not be so benign? - To Sean, posted by Scott L. Schofield on April 17, 2000, at 8:35:14
Well, here's what I understand (from Cooper, Bloom,
and Roth's Biochemical Basic of Neuropharmacology):- 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 structures- chronic presence of TCA's increases the responsiveness
of the POST-synaptic 5-HT autoreceptorsIn 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.From a subjective viewpoint, having taken medications
from both classes for years, I can certainly say
that they *feel* very different in terms of the
antidepressant effect and the side effects most
people have are different.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. Since this entire
subject started with a person asking about MDMA
neurotoxicity, might this person now argue that because
Prozac and MDMA both generate similar neuron changes,
but since we've used TCA's for 40 years without problems
it should be fine to take MDMA?Of course not.
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...As far as the "corscrew neurons" debacle, how would everybody
feel if scientists did NOT explore the reasons
behind it? I would be very concerned. It could be a problem
or it might not. My guess is that we simply don't
know yet.Sean.
> >
> > > well, I did some homework on this and TCA's and
> > > SRI's bind different locations of the serotonin
> > > neurons. both increase net serotonin transmission
> > > but by different means.
> > >
> > > sean
> >
> > Sean - I find the above to be a very interesting statement.
> >
> > *Could you please supply the references to back up your claims of TCAs bind to different serotonin receptors than the SSRIs?*
> >
> > I was under the impression that the TCAs bound to (and affected) mainly five different receptors (serotonin reuptake, norepinephrine reuptake, muscarinic/cholinergic, alpha-adrenergic and the histamine-H1 receptors). The SSRIs, to varying degrees also bind to some of these receptors, but not usually to an appreciable extent. I thought that the TCAs and SSRIs affected the same serotonin receptors. There are at least 15 different serotonin receptor subtypes, but I have not heard of any currently marketed antidepressant to adversely affect any of these.
> >
> > If you have found some new information about TCAs bind to different serotonergic receptors, I am very much interested. This may change our thinking on the long term effects of other serotonergic drugs (eg buspirone, LSD, Imitrex, etc.).
> >
> > This would be ground-breaking information that I think the whole scientific community will need to embrace. Hoping to hear from you soon.
> >
> > Sincerely - Cam W.
>
>
> The receptor site for reuptake blockade is the membrane reuptake transporter protein of the presynaptic neuron. This site serves an entirely different function than those receptors usually referred to on this board. The transporter acts as a shuttle to bring the released neurotransmitter back into the interior of the presynaptic neuron so that it can be used again. If a very "sticky" molecule (drug) "sits" on the "seat" of the "shuttle" and refuses to give it up, it prevents the neurotransmitter from getting its "ride" back into the cell.
>
> I know that there are subtle differences between some of the dopamine transporters. Perhaps the same is true of serotonin reuptake transporters. My guess is that any such differences in serotonin transporter, should they exist, are not significant with respect to the actions of these drugs to inhibit reuptake. Not sure.
>
> Although the sites on the transporter where both the neurotransmitter and drug bind are technically receptors, it may be clearer to state that they "bind to the reuptake transporter", so as not to confuse this action with those that effect neuron stimulation and regulation.
>
>
> - Scott
poster:Sean
thread:29745
URL: http://www.dr-bob.org/babble/20000411/msgs/30339.html