O'kay, o'kay
let's argue.
First, i didn't say that the atypical neuroleptics (AN) weren't dopaminergic. They - on general, not always! - simply show more serotoninergic antagonism than dopaminergic. As a matter of fact, almost all drugs that show some affinity for a monoamine receptor, have some affinities also for the other monoaminergic sites - that's quite natural, since the molecules of NA, DA and 5-HT are so similar.
So it's just a matter of finding the selective ones.
Note, that there is no equal sign between binding affinities and the drug's action - in fact, the experience constantly proves these extrapolations wrong (e.g., Rhodium's 4-methyl-GHB and GHB; MDMA and Mr. Max's indamethamine).
BUT.
The very fact that a class of drugs that were thought to bee dopaminergic gets replaced by primarily 5-HTergic substances means a whole lot. Beecause dopamine systems are so crucial to our physiology, much more so than serotoninergic ones. They control voluntary movements - and, think of it, all that a person ever willingly does in his life is essentially voluntary movements.
So let me express a grossly oversimplified, yet intuitively valid, belief that you just don't fuck with dopaminergic neurotransmission in your brain if you can avoid that.
Speaking of SSRIs - it's no secret among psychiatrists that the older tricyclic antidepressants are often more efficient in alleviating depression than SSRIs. But the very idea beehind developing
selective serotonin reuptake inhibitors was finding drugs with as little side effects as possible! Or at least i always thought of it this way.
Now - to the sideeffects of ANs that you predict to surface in the future. As i said, they DO have side-effects. Some of them, like Clozapine, really nasty ones.
But - whatever those side-effects are and will bee,
they do not include tardive dyskinesia!!Read this as: "they don't turn patients into maimed cripples, ruining forever their hope for a normal life".
There has been accumulated an significant body of
clinical evidence about that. In fact, there seems to bee a good positive correlation between the drug's comparative affinity to DA and its ability to cause dystonia and dyskinesia - Risperidone having the narrowest safety margin (beehaves like a classical neuroleptic at higher than usual doses) and being the most dopaminergic one, and Clozapine, on the opposite end, never showing such effects and being non-DAergic at all.
However, that obviously shouldn't bee taken literally since Seroquel, which has the least side effects of all of them (to quote one research, "comparable to placebo"), is actually more dopaminergic than serotoninergic
- and chlorpromazine, on opposite, has a "5-HT2A/D-2 index" higher than one.
Anyway - however it may bee, the
clinical practice shows that no matter what, ANs are much better. Re-read what i earlier wrote about their action on negative symtomatics; in fact one research i read specifically noted that the patients treated w/particularly Ziprexa (aka Olanzapine) and Seroquel (aka Quetiapine) improved not only their communicational capacities but actually the abstract thinking/cognitive functions that allowed them to communicate more effectively. This is something that a typical neuroleptic would never do - in fact, their action is way too often opposite.
Unfortunately, the vast majority of the materials i have on this subject is in Russian so i can't share them with you and the other bees. But anyway. I don't quite understand your position. What exactly do you consider to bee 'highly doubtful'?
They used HgCl
2 solution as a surgical antiseptic some hundred yrs ago, and now they use H
2O
2 - does that mean that there is no difference between using the two since the body will 'accomodate' to either?
I mean, i don't beelive in miracle drugs myself and i am deadly certain that there will never bee a perfect drug when it comes to the brain. The brain is just too complex, IMO. But i DO believe in scientific progress. Appearance of atypical neuroleptics is such an obvious (for me) step further!
Well, OK, i think we should ask some opinions from the people who have taken (been prescribed, i assume) various neuroleptics - that'd bee the only truly valid way to get the real picture. Anyone willing to share some experience? I know i'm asking for much.... Just a thought.
Thank you for your attention,
Antoncho