Posted by Dragon Black on September 4, 2007, at 20:17:34
In reply to Re: Anyone speak French? Please interpret Dr.'s e, posted by sam123 on September 2, 2007, at 12:19:02
Hmm, maybe, but I don’t think so. Yes, tianeptine is structurally similar to the TCAs, in that the molecule has 3 rings, but that’s where the similarities end. I think what it does is bound to be more important, and the mechanism of action of tianeptine is opposite the TCAs – it enhances the reuptake of serotonin while the TCAs inhibit the reuptake of one or more monoamines. So I’ve surmised that one of the following must be the reason that Servier, the make of tianeptine, has contraindicated MAOIs:
1. Serotonin Syndrome – that even though it’s the anti-SSRI, its still serotonergic in nature and therefore they don’t want people messing with multiple serotonergic agents. Whether this is a legitimate fear is a question out of my league, but I suspect it is not. It is worth noting, however, that like fluoxetine, tianeptine increases serotonin innervation in the forebrain. http://www.tianeptine.com/forebrain.html More interesting is the fact that on their website, they list MAOIs under “Contraindications,” but under “Drug Interactions” they get more specific and say “with nonselective MAOIs.” http://www.servier.com/pro/Neurosciences/stablon/stablon_spc.asp So maybe if we mess with type A we could have a problem, but to me it looks like low dose selegiline is in like slim.
2. Tianeptine increases extracellular dopamine in the nucleus accumbens. http://www.tianeptine.com/dopamine-nacc.html Since MAOIs inhibit dopamine deamination, and tend to be off limits with anything that touches dopamine, maybe this presents a problem. Again, I don’t really know but I doubt it.
3. They just didn’t study it enough and they don’t want to hassle with the possibility of liability. I can’t for the life of me find it now, but someone on here posted a while back that this is what his Dr. thought, that the Pharms just weren’t willing to countenance having an MAOI related lawsuit on their hands.
But who really knows, right? My guess is no one, even in the research community. In the end it’s, “Buy the ticket, ride the ride.”
> It is related to the TCA's, for which MAOI's are contraindicated:
>
> Complications
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> In most reports, serotonin syndrome has been mild to moderate in severity without medical complications. However, a distinct minority of cases, particularly those associated with MAOI-tricyclic and MAOI-SRI combinations and MDMA, were severe and some fatal. Overall, medical complications appear to be less common than in NMS. Rhabdomyolysis was the most common serious medical complication of serotonin syndrome, occurring in 45 (26.8%) cases. Myoglobinuria and renal failure were reported in 8 (4.8%) patients. Generalized seizures were reported in 18 (10.7%) cases, including 7 fatalities. Similarly, DIC occurred in 8 patients, 5 of whom died. Thus, although medical complications were not common in patients with serotonin syndrome, they were associated with a substantial mortality risk.
>
> ONSET AND PREDISPOSING FACTORS
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> Serotoninergic Medications
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> Nearly all medications that enhance CNS serotoninergic neurotransmission have been reported in association with cases of the serotonin syndrome (Table 3-1). Since the cases reviewed by Sternbach (1991), the most commonly implicated agents reported in subsequent case reports and case series have been combinations of MAOIs (reversible and irreversible) and tricyclics (N=18) and MAOIs and SRIs (N=34). These combinations also have been involved in 11 (61.1%) of the 18 fatal cases of serotonin syndrome. Serotonin syndrome has been reported when an MAOI was used in combination with L-tryptophan, dextromethorphan, or clonazepam. Tricyclics combined with alprazolam, amoxapine, SRIs, lithium, SRIs and lithium, trazodone and lithium, nefazodone and thioridazine, and m-chlorophenylpiperazine (m-CPP) also have been associated with the syndrome. SSRIs in combination with lithium, venlafaxine, buspirone, dextromethorphan, carbamazepine, clonazepam, mirtazapine, m-CPP, nefazodone, trazodone, risperidone, sumatriptan, dihydroergotamine and tramadol have been reported to produce serotonin syndrome. Combinations of nefazodone with trazodone, fluoxetine, valproate, and dothiepin have been reported.
>
> http://www.nmsis.org/Related_Syndromes.shtml
poster:Dragon Black
thread:779503
URL: http://www.dr-bob.org/babble/20070831/msgs/780858.html